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Journal of Cancer Research and Clinical Oncology
Published in: Journal of Cancer Research and Clinical Oncology 6/2016

01-06-2016 | Review – Cancer Research

Process of hepatic metastasis from pancreatic cancer: biology with clinical significance

Authors: Haojun Shi, Ji Li, Deliang Fu

Published in: Journal of Cancer Research and Clinical Oncology | Issue 6/2016

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Abstract

Purpose

Pancreatic cancer shows a remarkable preference for the liver to establish secondary tumors. Selective metastasis to the liver is attributed to the development of potential microenvironment for the survival of pancreatic cancer cells. This review aims to provide a full understanding of the hepatic metastatic process from circulating pancreatic cancer cells to their settlement in the liver, serving as a basic theory for efficient prediction and treatment of metastatic diseases.

Methods

A systematic search of relevant original articles and reviews was performed on PubMed, EMBASE and Cochrane Library for the purpose of this review.

Results

Three interrelated phases are delineated as the contributions of the interaction between pancreatic cancer cells and the liver to hepatic metastasis process. Chemotaxis of disseminated pancreatic cancer cells and simultaneous defensive formation of platelets or neutrophils facilitate specific metastasis toward the liver. Remodeling of extracellular matrix and stromal cells in hepatic lobules and angiogenesis induced by proangiogenic factors support the survival and growth of clinical micrometastasis colonizing the liver. The bimodal role of the immune system or prevalence of cancer cells over the immune system makes metastatic progression successfully proceed from micrometastasis to macrometastasis.

Conclusions

Pancreatic cancer is an appropriate research object of cancer metastasis representing more than a straight cascade. If any of the successive or simultaneous phases, especially tumor-induced immunosuppression, is totally disrupted, hepatic metastasis will be temporarily under control or even cancelled forever. To shrink cancers on multiple fronts and prolong survival for patients, novel oral or intravenous anti-cancer agents covering one or different phases of metastatic pancreatic cancer are expected to be integrated into innovative strategies on the premise of safety and efficacious biostability.
Literature
Abdelrahim M, Safe S (2005) Cyclooxygenase-2 inhibitors decrease vascular endothelial growth factor expression in colon cancer cells by enhanced degradation of Sp1 and Sp4 proteins. Mol Pharmacol 68(2):317–329PubMed
Abdelrahim M, Smith R 3rd, Burghardt R, Safe S (2004) Role of Sp proteins in regulation of vascular endothelial growth factor expression and proliferation of pancreatic cancer cells. Cancer Res 64(18):6740–6749PubMedCrossRef
Abdelrahim M, Baker CH, Abbruzzese JL, Safe S (2006) Tolfenamic acid and pancreatic cancer growth, angiogenesis, and Sp protein degradation. J Natl Cancer Inst 98(12):855–868PubMedCrossRef
Abdelrahim M, Baker CH, Abbruzzese JL, Sheikh-Hamad D, Liu S, Cho SD, Yoon K, Safe S (2007) Regulation of vascular endothelial growth factor receptor-1 expression by specificity proteins 1, 3, and 4 in pancreatic cancer cells. Cancer Res 67(7):3286–3294PubMedCrossRef
Airoldi I, Cocco C, Morandi F, Prigione I, Pistoia V (2008) CXCR5 may be involved in the attraction of human metastatic neuroblastoma cells to the bone marrow. Cancer Immunol Immunother 57(4):541–548PubMedCrossRef
Amedei A, Niccolai E, Benagiano M, Della Bella C, Cianchi F, Bechi P, Taddei A, Bencini L, Farsi M, Cappello P, Prisco D, Novelli F, D’Elios MM (2013) Ex vivo analysis of pancreatic cancer-infiltrating T lymphocytes reveals that ENO-specific Tregs accumulate in tumor tissue and inhibit Th1/Th17 effector cell functions. Cancer Immunol Immunother 62(7):1249–1260PubMedCrossRef
American Cancer Society (2014) Cancer facts and figures 2014. American Cancer Society, Atlanta
Ando K, Takahashi F, Motojima S, Nakashima K, Kaneko N, Hoshi K, Takahashi K (2013) Possible role for tocilizumab, an anti-interleukin-6 receptor antibody, in treating cancer cachexia. J Clin Oncol 31(6):e69–e72PubMedCrossRef
Aosasa S, Ono S, Mochizuki H, Tsujimoto H, Osada S, Takayama E, Seki S, Hiraide H (2000) Activation of monocytes and endothelial cells depends on the severity of surgical stress. World J Surg 24(1):10–16PubMedCrossRef
Aspinall AI, Curbishley SM, Lalor PF, Weston CJ, Blahova Miroslava, Liaskou E, Adams RM, Holt AP, Adams DH (2010) CX(3)CR1 and vascular adhesion protein-1-dependent recruitment of CD16(+) monocytes across human liver sinusoidal endothelium. Hepatology 51(6):2030–2039PubMedPubMedCentralCrossRef
Aviezer D, Cotton S, David M, Segev A, Khaselev N, Galili N, Gross Z, Yayon A (2000) Porphyrin analogues as novel antagonists of fibroblast growth factor and vascular endothelial growth factor receptor binding that inhibit endothelial cell proliferation, tumor progression, and metastasis. Cancer Res 60(11):2973–2980PubMed
Bachelerie F, Ben-Baruch A, Burkhardt AM, Combadiere C, Farber JM, Graham GJ, Horuk R, Sparre-Ulrich AH, Locati M, Luster AD, Mantovani A, Matsushima K, Murphy PM, Nibbs R, Nomiyama H, Power CA, Proudfoot AE, Rosenkilde MM, Rot A, Sozzani S, Thelen M, Yoshie O, Zlotnik A (2013) International Union of Basic and Clinical Pharmacology. LXXXIX. Update on the extended family of chemokine receptors and introducing a new nomenclature for atypical chemokine receptors. Pharmacol Rev 66(1):1–79PubMedCrossRef
Banerjee T, Duhadaway JB, Gaspari P, Sutanto-Ward E, Munn DH, Mellor AL, Malachowski WP, Prendergast GC, Muller AJ (2008) A key in vivo antitumor mechanism of action of natural product-based brassinins is inhibition of indoleamine 2,3-dioxygenase. Oncogene 27(20):2851–2857PubMedCrossRef
Baribaud F, Edwards TG, Sharron M, Brelot A, Heveker N, Price K, Mortari F, Alizon M, Tsang M, Doms RW (2001) Antigenically distinct conformations of CXCR4. J Virol 75(19):8957–8967PubMedPubMedCentralCrossRef
Bausch D, Pausch T, Krauss T, Hopt UT, Fernandez-del-Castillo C, Warshaw AL, Thayer SP, Keck T (2011) Neutrophil granulocyte derived MMP-9 is a VEGF independent functional component of the angiogenic switch in pancreatic ductal adenocarcinoma. Angiogenesis 14(3):235–243PubMedPubMedCentralCrossRef
Beauchamp RD, Lyons RM, Yang EY, Coffey RJ Jr, Moses HL (1990) Expression of and response to growth regulatory peptides by two human pancreatic carcinoma cell lines. Pancreas 5(4):369–380PubMedCrossRef
Benson DD, Meng X, Fullerton DA, Moore EE, Lee JH, Ao L, Silliman CC, Barnett CC Jr (2012) Activation state of stromal inflammatory cells in murine metastatic pancreatic adenocarcinoma. Am J Physiol Regul Integr Comp Physiol 302(9):R1067–R1075PubMedPubMedCentralCrossRef
Biswas SK, Mantovani A (2010) Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol 11(10):889–896PubMedCrossRef
Blank C, Kuball J, Voelkl S, Wiendl H, Becker B, Walter B, Majdic O, Gajewski TF, Theobald M, Andreesen R, Mackensen A (2006) Blockade of PD-L1 (B7-H1) augments human tumor-specific T cell responses in vitro. Int J Cancer 119(2):317–327PubMedCrossRef
Boldajipour B, Mahabaleshwar H, Kardash E, Reichman-Fried M, Blaser H, Minina S, Wilson D, Xu Q, Raz E (2008) Control of chemokine-guided cell migration by ligand sequestration. Cell 132(3):463–473PubMedCrossRef
Bourd-Boittin K, Basset L, Bonnier D, L’helgoualc’h A, Samson M, Théret N (2009) CX3CL1/fractalkine shedding by human hepatic stellate cells: contribution to chronic inflammation in the liver. J Cell Mol Med 13(8A):1526–1535PubMedPubMedCentralCrossRef
Brennecke P, Arlt MJ, Campanile C, Husmann K, Gvozdenovic A, Apuzzo T, Thelen M, Born W, Fuchs B (2014) CXCR4 antibody treatment suppresses metastatic spread to the lung of intratibial human osteosarcoma xenografts in mice. Clin Exp Metastasis 31(3):339–349PubMedPubMedCentralCrossRef
Brodt P, Fallavollita L, Bresalier RS, Meterissian S, Norton CR, Wolitzky BA (1997) Liver endothelial E-selectin mediates carcinoma cell adhesion and promotes liver metastasis. Int J Cancer 71(4):612–619PubMedCrossRef
Brown KM, Domin C, Aranha GV, Yong S, Shoup M (2005) Increased preoperative platelet count is associated with decreased survival after resection for adenocarcinoma of the pancreas. Am J Surg 189(3):278–282PubMedCrossRef
Bürkle A, Niedermeier M, Schmitt-Gräff A, Wierda WG, Keating MJ, Burger JA (2007) Overexpression of the CXCR5 chemokine receptor, and its ligand, CXCL13 in B-cell chronic lymphocytic leukemia. Blood 110(9):3316–3325PubMedCrossRef
Burns JM, Dairaghi DJ, Deitz M, Tsang M, Schall TJ (2002) Comprehensive mapping of poxvirus vCCI chemokine-binding protein. Expanded range of ligand interactions and unusual dissociation kinetics. J Biol Chem 277(4):2785–2789PubMedCrossRef
Burns JM, Summers BC, Wang Y, Melikian A, Berahovich R, Miao Z, Penfold ME, Sunshine MJ, Littman DR, Kuo CJ, Wei K, McMaster BE, Wright K, Howard MC, Schall TJ (2006) A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development. J Exp Med 203(9):2201–2213PubMedPubMedCentralCrossRef
Bursill CA, Cash JL, Channon KM, Greaves DR (2006) Membrane-bound CC chemokine inhibitor 35 K provides localized inhibition of CC chemokine activity in vitro and in vivo. J Immunol 177(8):5567–5573PubMedCrossRef
Cady SG, Sono M (1991) 1-Methyl-dl-tryptophan, beta-(3-benzofuranyl)-dl-alanine (the oxygen analog of tryptophan), and beta-[3-benzo(b)thienyl]-dl-alanine (the sulfur analog of tryptophan) are competitive inhibitors for indoleamine 2,3-dioxygenase. Arch Biochem Biophys 291(2):326–333PubMedCrossRef
Cambien B, Richard-Fiardo P, Karimdjee BF, Martini V, Ferrua B, Pitard B, Schmid-Antomarchi H, Schmid-Alliana A (2011) CCL5 neutralization restricts cancer growth and potentiates the targeting of PDGFRβ in colorectal carcinoma. PLoS ONE 6(12):e28842PubMedPubMedCentralCrossRef
Cappello P, Tomaino B, Chiarle R, Ceruti P, Novarino A, Castagnoli C, Migliorini P, Perconti G, Giallongo A, Milella M, Monsurrò V, Barbi S, Scarpa A, Nisticò P, Giovarelli M, Novelli F (2009) An integrated humoral and cellular response is elicited in pancreatic cancer by alpha-enolase, a novel pancreatic ductal adenocarcinoma-associated antigen. Int J Cancer 125(3):639–648PubMedCrossRef
Cardillo TM, Ying Z, Gold DV (2001) Therapeutic advantage of (90)yttrium- versus (131)iodine-labeled PAM4 antibody in experimental pancreatic cancer. Clin Cancer Res 7(10):3186–3192PubMed
Celesti G, Di Caro G, Bianchi P, Grizzi F, Marchesi F, Basso G, Rahal D, Delconte G, Catalano M, Cappello P, Roncalli M, Zerbi A, Montorsi M, Novelli F, Mantovani A, Allavena P, Malesci A, Laghi L (2013) Early expression of the fractalkine receptor CX3CR1 in pancreatic carcinogenesis. Br J Cancer 109(9):2424–2433PubMedPubMedCentralCrossRef
Chari A, Pri-Chen H, Jagannath S (2013) Complete remission achieved with single agent CNTO 328, an anti-IL-6 monoclonal antibody, in relapsed and refractory myeloma. Clin Lymphoma Myeloma Leuk 13(3):333–337PubMedCrossRef
Chase SD, Magnani JL, Simon SI (2012) E-selectin ligands as mechanosensitive receptors on neutrophils in health and disease. Ann Biomed Eng 40(4):849–859PubMedPubMedCentralCrossRef
Clark CE, Hingorani SR, Mick R, Combs C, Tuveson DA, Vonderheide RH (2007) Dynamics of the immune reaction to pancreatic cancer from inception to invasion. Cancer Res 67(19):9518–9527PubMedCrossRef
Connolly MK, Mallen-St Clair J, Bedrosian AS, Malhotra A, Vera V, Ibrahim J, Henning J, Pachter HL, Bar-Sagi D, Frey AB, Miller G (2010) Distinct populations of metastases-enabling myeloid cells expand in the liver of mice harboring invasive and preinvasive intra-abdominal tumor. J Leukoc Biol 87(4):713–725PubMedPubMedCentralCrossRef
Dambly-Chaudière C, Cubedo N, Ghysen A (2007) Control of cell migration in the development of the posterior lateral line: antagonistic interactions between the chemokine receptors CXCR4 and CXCR7/RDC1. BMC Dev Biol 7:23PubMedPubMedCentralCrossRef
Dambrauskas Z, Svensson H, Joshi M, Hyltander A, Naredi P, Iresjö BM (2014) Expression of major histocompatibility complex class I-related chain A/B (MICA/B) in pancreatic carcinoma. Int J Oncol 44(1):99–104PubMed
Danielczyk A, Stahn R, Faulstich D, Löffler A, Märten A, Karsten U, Goletz S (2006) PankoMab: a potent new generation anti-tumour MUC1 antibody. Cancer Immunol Immunother 55(11):1337–1347PubMedCrossRef
Décaillot FM, Kazmi MA, Lin Y, Ray-Saha S, Sakmar TP, Sachdev P (2011) CXCR7/CXCR4 heterodimer constitutively recruits beta-arrestin to enhance cell migration. J Biol Chem 286(37):32188–32197PubMedPubMedCentralCrossRef
Degen JL, Palumbo JS (2012) Hemostatic factors, innate immunity and malignancy. Thromb Res 129(Suppl 1):S1–S5PubMedCrossRef
DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, Alteri R, Robbins AS (2014) Jemal A (2014) Cancer treatment and survivorship statistics. CA Cancer J Clin 64(4):252–271PubMedCrossRef
Deshane J, Garner CC, Sontheimer H (2003) Chlorotoxin inhibits glioma cell invasion via matrix metalloproteinase-2. J Biol Chem 278(6):4135–4144PubMedCrossRef
Dickson MC, Martin JS, Cousins FM, Kulkarni AB, Karlsson S, Akhurst RJ (1995) Defective haematopoiesis and vasculogenesis in transforming growth factor-beta 1 knock out mice. Development 121(6):1845–1854PubMed
Dong C, Slattery MJ, Rank BM, You J (2002) In vitro characterization and micromechanics of tumor cell chemotactic protrusion, locomotion, and extravasation. Ann Biomed Eng 30(3):344–355PubMedPubMedCentralCrossRef
Dotor J, López-Vázquez AB, Lasarte JJ, Sarobe P, García-Granero M, Riezu-Boj JI, Martínez A, Feijoó E, López-Sagaseta J, Hermida J, Prieto J, Borrás-Cuesta F (2007) Identification of peptide inhibitors of transforming growth factor beta 1 using a phage-displayed peptide library. Cytokine 39(2):106–115PubMedCrossRef
Dziadek S, Kunz H (2004) Synthesis of tumor-associated glycopeptide antigens for the development of tumor-selective vaccines. Chem Rec 3(6):308–321PubMedCrossRef
Efsen E, Grappone C, DeFranco RM, Milani S, Romanelli RG, Bonacchi A, Caligiuri A, Failli P, Annunziato F, Pagliai G, Pinzani M, Laffi G, Gentilini P, Marra F (2002) Up-regulated expression of fractalkine and its receptor CX3CR1 during liver injury in humans. J Hepatol 37(1):39–47PubMedCrossRef
El Haibi CP, Sharma PK, Singh R, Johnson PR, Suttles J, Singh S, Lillard JW Jr (2010) PI3Kp110-, Src-, FAK-dependent and DOCK2-independent migration and invasion of CXCL13-stimulated prostate cancer cells. Mol Cancer 9:85PubMedPubMedCentralCrossRef
El Kholy NM, Sallam MM, Ahmed MB, Sallam RM, Asfour IA, Hammouda JA, Habib HZ, Abu-Zahra F (2011) Expression of indoleamine 2,3-dioxygenase in acute myeloid leukemia and the effect of its inhibition on cultured leukemia blast cells. Med Oncol 28(1):270–278PubMedCrossRef
El-Ghlban S, Kasai T, Shigehiro T, Yin HX, Sekhar S, Ida M, Sanchez A, Mizutani A, Kudoh T, Murakami H, Seno M (2014) Chlorotoxin-Fc fusion inhibits release of MMP-2 from pancreatic cancer cells. Biomed Res Int 2014:152659PubMedPubMedCentralCrossRef
Erkan M, Hausmann S, Michalski CW, Fingerle AA, Dobritz M, Kleeff J, Friess H (2012) The role of stroma in pancreatic cancer: diagnostic and therapeutic implications. Nat Rev Gastroenterol Hepatol 9(8):454–467PubMedCrossRef
Ewing J (1928) Neoplastic diseases, 6th edn. W. B. Sanders, Philadelphia
Fallarino F, Grohmann U, You S, McGrath BC, Cavener DR, Vacca C, Orabona C, Bianchi R, Belladonna ML, Volpi C, Santamaria P, Fioretti MC, Puccetti P (2006) The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells. J Immunol 176(11):6752–6761PubMedCrossRef
Fannon M, Forsten-Williams K, Nugent MA, Gregory KJ, Chu CL, Goerges-Wildt AL, Panigrahy D, Kaipainen A, Barnes C, Lapp C, Shing Y (2008) Sucrose octasulfate regulates fibroblast growth factor-2 binding, transport, and activity: potential for regulation of tumor growth. J Cell Physiol 215(2):434–441PubMedPubMedCentralCrossRef
Faouzi S, Lepreux S, Bedin C, Dubuisson L, Balabaud C, Bioulac-Sage P, Desmoulière A, Rosenbaum J (1999) Activation of cultured rat hepatic stellate cells by tumoral hepatocytes. Lab Invest 79(4):485–493PubMed
Ferro V, Dredge K, Liu L, Hammond E, Bytheway I, Li C, Johnstone K, Karoli T, Davis K, Copeman E, Gautam A (2007) PI-88 and novel heparan sulfate mimetics inhibit angiogenesis. Semin Thromb Hemost 33(5):557–568
Fong AM, Premont RT, Richardson RM, Yu YR, Lefkowitz RJ, Patel DD (2002) Defective lymphocyte chemotaxis in beta-arrestin2- and GRK6-deficient mice. Proc Natl Acad Sci U S A 99(11):7478–7483PubMedPubMedCentralCrossRef
Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Malenkovich N, Okazaki T, Byrne MC, Horton HF, Fouser L, Carter L, Ling V, Bowman MR, Carreno BM, Collins M, Wood CR, Honjo T (2000) Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 192(7):1027–1034PubMedPubMedCentralCrossRef
Freitas C, Desnoyer A, Meuris F, Bachelerie F, Balabanian K, Machelon V (2014) The relevance of the chemokine receptor ACKR3/CXCR7 on CXCL12-mediated effects in cancers with a focus on virus-related cancers. Cytokine Growth Factor Rev 25(3):307–316PubMedCrossRef
Fridlender ZG, Sun J, Kim S, Kapoor V, Cheng G, Ling L, Worthen GS, Albelda SM (2009) Polarization of tumor-associated neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN. Cancer Cell 16(3):183–194PubMedPubMedCentralCrossRef
Fukunaga A, Miyamoto M, Cho Y, Murakami S, Kawarada Y, Oshikiri T, Kato K, Kurokawa T, Suzuoki M, Nakakubo Y, Hiraoka K, Itoh T, Morikawa T, Okushiba S, Kondo S, Katoh H (2004) CD8+ tumor-infiltrating lymphocytes together with CD4+ tumor-infiltrating lymphocytes and dendritic cells improve the prognosis of patients with pancreatic adenocarcinoma. Pancreas 28(1):e26–e31PubMedCrossRef
Galustian C, Childs RA, Stoll M, Ishida H, Kiso M, Feizi T (2002) Synergistic interactions of the two classes of ligand, sialyl-Lewis(a/x) fuco-oligosaccharides and short sulpho-motifs, with the P- and L-selectins: implications for therapeutic inhibitor designs. Immunology 105(3):350–359PubMedPubMedCentralCrossRef
Gastpar H, Ambrus JL, Ambrus CM (1982) Platelet cancer cell interaction in metastasis formation. Platelet aggregation inhibitors: a possible approach to metastasis prevention. Prog Clin Biol Res 89:63–82PubMed
Gebauer F, Wicklein D, Stübke K, Nehmann N, Schmidt A, Salamon J, Peldschus K, Nentwich MF, Adam G, Tolstonog G, Bockhorn M, Izbicki JR, Wagener C, Schumacher U (2013) Selectin binding is essential for peritoneal carcinomatosis in a xenograft model of human pancreatic adenocarcinoma in pfp–/rag2– mice. Gut 62(5):741–750PubMedCrossRef
Gil-Guerrero L, Dotor J, Huibregtse IL, Casares N, López-Vázquez AB, Rudilla F, Riezu-Boj JI, López-Sagaseta J, Hermida J, Van Deventer S, Bezunartea J, Llopiz D, Sarobe P, Prieto J, Borrás-Cuesta F, Lasarte JJ (2008) In vitro and in vivo down-regulation of regulatory T cell activity with a peptide inhibitor of TGF-beta1. J Immunol 181(1):126–135PubMedCrossRef
Gold DV, Cardillo T, Goldenberg DM, Sharkey RM (2001) Localization of pancreatic cancer with radiolabeled monoclonal antibody PAM4. Crit Rev Oncol Hematol 39(1–2):147–154PubMedCrossRef
Goydos JS, Elder E, Whiteside TL, Finn OJ, Lotze MT (1996) A phase I trial of a synthetic mucin peptide vaccine. Induction of specific immune reactivity in patients with adenocarcinoma. J Surg Res 63(1):298–304PubMedCrossRef
Gravel S, Malouf C, Boulais PE, Berchiche YA, Oishi S, Fujii N, Leduc R, Sinnett D, Heveker N (2010) The peptidomimetic CXCR4 antagonist TC14012 recruits beta-arrestin to CXCR7: roles of receptor domains. J Biol Chem 285(49):37939–37943PubMedPubMedCentralCrossRef
Grymula K, Tarnowski M, Wysoczynski M, Drukala J, Barr FG, Ratajczak J, Kucia M, Ratajczak MZ (2010) Overlapping and distinct role of CXCR7-SDF-1/ITAC and CXCR4-SDF-1 axes in regulating metastatic behavior of human rhabdomyosarcomas. Int J Cancer 127(11):2554–2568PubMedPubMedCentralCrossRef
Gulec SA, Cohen SJ, Pennington KL, Zuckier LS, Hauke RJ, Horne H, Wegener WA, Teoh N, Gold DV, Sharkey RM, Goldenberg DM (2011) Treatment of advanced pancreatic carcinoma with 90Y-Clivatuzumab Tetraxetan: a phase I single-dose escalation trial. Clin Cancer Res 17(12):4091–4100PubMedPubMedCentralCrossRef
Guleng B, Tateishi K, Ohta M, Kanai F, Jazag A, Ijichi H, Tanaka Y, Washida M, Morikane K, Fukushima Y, Yamori T, Tsuruo T, Kawabe T, Miyagishi M, Taira K, Sata M, Omata M (2005) Blockade of the stromal cell-derived factor-1/CXCR4 axis attenuates in vivo tumor growth by inhibiting angiogenesis in a vascular endothelial growth factor-independent manner. Cancer Res 65(13):5864–5871PubMedCrossRef
Hanaoka H, Mukai T, Tamamura H, Mori T, Ishino S, Ogawa K, Iida Y, Doi R, Fujii N, Saji H (2006) Development of a 111In-labeled peptide derivative targeting a chemokine receptor, CXCR4, for imaging tumors. Nucl Med Biol 33(4):489–494PubMedCrossRef
Haq M, Shafii A, Zervos EE, Rosemurgy AS (2000) Addition of matrix metalloproteinase inhibition to conventional cytotoxic therapy reduces tumor implantation and prolongs survival in a murine model of human pancreatic cancer. Cancer Res 60(12):3207–3211PubMed
Hassan S, Buchanan M, Jahan K, Aguilar-Mahecha A, Gaboury L, Muller WJ, Alsawafi Y, Mourskaia AA, Siegel PM, Salvucci O, Basik M (2011) CXCR4 peptide antagonist inhibits primary breast tumor growth, metastasis and enhances the efficacy of anti-VEGF treatment or docetaxel in a transgenic mouse model. Int J Cancer 129(1):225–232PubMedCrossRef
Hattermann K, Mentlein R (2013) An infernal trio: the chemokine CXCL12 and its receptors CXCR4 and CXCR7 in tumor biology. Ann Anat 195(2):103–110PubMedCrossRef
Hattermann K, Held-Feindt J, Lucius R, Müerköster SS, Penfold ME, Schall TJ, Mentlein R (2010) The chemokine receptor CXCR7 is highly expressed in human glioma cells and mediates antiapoptotic effects. Cancer Res 70(8):3299–3308PubMedCrossRef
He Y, Song W, Lei J, Li Z, Cao J, Huang S, Meng J, Xu H, Jin Z, Xue H (2012) Anti-CXCR4 monoclonal antibody conjugated to ultrasmall superparamagnetic iron oxide nanoparticles in an application of MR molecular imaging of pancreatic cancer cell lines. Acta Radiol 53(9):1049–1058PubMedCrossRef
Hendrix CW, Collier AC, Lederman MM, Schols D, Pollard RB, Brown S, Jackson JB, Coombs RW, Glesby MJ, Flexner CW, Bridger GJ, Badel K, MacFarland RT, Henson GW, Calandra G; AMD3100 HIV Study Group (2004) Safety, pharmacokinetics, and antiviral activity of AMD3100, a selective CXCR4 receptor inhibitor, in HIV-1 infection. J Acquir Immune Defic Syndr 37(2):1253–1262CrossRef
Hernandez L, Magalhaes MA, Coniglio SJ, Condeelis JS, Segall JE (2011) Opposing roles of CXCR4 and CXCR7 in breast cancer metastasis. Breast Cancer Res 13(6):R128PubMedPubMedCentralCrossRef
Higashi K, Asano K, Yagi M, Yamada K, Arakawa T, Ehashi T, Mori T, Sumida K, Kushida M, Ando S, Kinoshita M, Kakehi K, Tachibana T, Saito K (2014) Expression of the clustered NeuAcα2-3Galβ O-glycan determines the cell differentiation state of the cells. J Biol Chem 289(37):25833–25843PubMedPubMedCentralCrossRef
Hiraoka N, Onozato K, Kosuge T, Hirohashi S (2006) Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions. Clin Cancer Res 12(18):5423–5434PubMedCrossRef
Honn KV, Tang DG, Crissman JD (1992) Platelets and cancer metastasis: a causal relationship? Cancer Metastasis Rev 11(3–4):325–351PubMedCrossRef
Hou DY, Muller AJ, Sharma MD, DuHadaway J, Banerjee T, Johnson M, Mellor AL, Prendergast GC, Munn DH (2007) Inhibition of indoleamine 2,3-dioxygenase in dendritic cells by stereoisomers of 1-methyl-tryptophan correlates with antitumor responses. Cancer Res 67(2):792–801PubMedCrossRef
Iacobuzio-Donahue CA, Fu B, Yachida S, Luo M, Abe H, Henderson CM, Vilardell F, Wang Z, Keller JW, Banerjee P, Herman JM, Cameron JL, Yeo CJ, Halushka MK, Eshleman JR, Raben M, Klein AP, Hruban RH, Hidalgo M, Laheru D (2009) DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol 27(11):1806–1813PubMedPubMedCentralCrossRef
Ikemoto T, Yamaguchi T, Morine Y, Imura S, Soejima Y, Fujii M, Maekawa Y, Yasutomo K, Shimada M (2006) Clinical roles of increased populations of Foxp3+ CD4+ T cells in peripheral blood from advanced pancreatic cancer patients. Pancreas 33(4):386–390PubMedCrossRef
Iki K, Tsutsumi M, Kido A, Sakitani H, Takahama M, Yoshimoto M, Motoyama M, Tatsumi K, Tsunoda T, Konishi Y (1999) Expression of matrix metalloproteinase 2 (MMP-2), membrane-type 1 MMP and tissue inhibitor of metalloproteinase 2 and activation of proMMP-2 in pancreatic duct adenocarcinomas in hamsters treated with N-nitrosobis(2-oxopropyl)amine. Carcinogenesis 20(7):1323–1329PubMedCrossRef
Imamura T, Iguchi H, Manabe T, Ohshio G, Yoshimura T, Wang ZH, Suwa H, Ishigami S, Imamura M (1995) Quantitative analysis of collagen and collagen subtypes I, III, and V in human pancreatic cancer, tumor-associated chronic pancreatitis, and alcoholic chronic pancreatitis. Pancreas 11(4):357–364PubMedCrossRef
Ino Y, Yamazaki-Itoh R, Shimada K, Iwasaki M, Kosuge T, Kanai Y, Hiraoka N (2013) Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer. Br J Cancer 108(4):914–923PubMedPubMedCentralCrossRef
Ischenko I, Guba M, Yezhelyev M, Papyan A, Schmid G, Green T, Fennell M, Jauch KW, Bruns CJ (2007) Effect of Src kinase inhibition on metastasis and tumor angiogenesis in human pancreatic cancer. Angiogenesis 10(3):167–182PubMedCrossRef
Iwamura T, Caffrey TC, Kitamura N, Yamanari H, Setoguchi T, Hollingsworth MA (1997) P-selectin expression in a metastatic pancreatic tumor cell line (SUIT-2). Cancer Res 57(6):1206–1212PubMed
Jähnichen S, Blanchetot C, Maussang D, Gonzalez-Pajuelo M, Chow KY, Bosch L, De Vrieze S, Serruys B, Ulrichts H, Vandevelde W, Saunders M, De Haard HJ, Schols D, Leurs R, Vanlandschoot P, Verrips T, Smit MJ (2010) CXCR4 nanobodies (VHH-based single variable domains) potently inhibit chemotaxis and HIV-1 replication and mobilize stem cells. Proc Natl Acad Sci U S A 107(47):20565–20570PubMedPubMedCentralCrossRef
Ji SQ, Cao J, Zhang QY, Li YY, Yan YQ, Yu FX (2013) Adipose tissue-derived stem cells promote pancreatic cancer cell proliferation and invasion. Braz J Med Biol Res 46(9):758–764PubMedPubMedCentralCrossRef
Justinger C, Schlüter C, Oliviera-Frick V, Kopp B, Rubie C, Schilling MK (2008) Increased growth factor expression after hepatic and pancreatic resection. Oncol Rep 20(6):1527–1531PubMed
Kalatskaya I, Berchiche YA, Gravel S, Limberg BJ, Rosenbaum JS, Heveker N (2009) AMD3100 is a CXCR7 ligand with allosteric agonist properties. Mol Pharmacol 75(5):1240–1247PubMedCrossRef
Kamisawa T, Isawa T, Koike M, Tsuruta K, Okamoto A (1995) Hematogenous metastases of pancreatic ductal carcinoma. Pancreas 11(4):345–349PubMedCrossRef
Kashima K, Watanabe M, Sato Y, Hata J, Ishii N, Aoki Y (2014) Inhibition of metastasis of rhabdomyosarcoma by a novel neutralizing antibody to CXC chemokine receptor-4. Cancer Sci 105(10):1343–1350PubMedPubMedCentralCrossRef
Khatib AM, Auguste P, Fallavollita L, Wang N, Samani A, Kontogiannea M, Meterissian S, Brodt P (2005) Characterization of the host proinflammatory response to tumor cells during the initial stages of liver metastasis. Am J Pathol 167(3):749–759PubMedPubMedCentralCrossRef
Kilian M, Gregor JI, Heukamp I, Hanel M, Ahlgrimm M, Schimke I, Kristiansen G, Ommer A, Walz MK, Jacobi CA, Wenger FA (2006) Matrix metalloproteinase inhibitor RO 28-2653 decreases liver metastasis by reduction of MMP-2 and MMP-9 concentration in BOP-induced ductal pancreatic cancer in Syrian Hamsters: inhibition of matrix metalloproteinases in pancreatic cancer. Prostaglandins Leukot Essent Fatty Acids 75(6):429–434PubMedCrossRef
Kim SY, Lee CH, Midura BV, Yeung C, Mendoza A, Hong SH, Ren L, Wong D, Korz W, Merzouk A, Salari H, Zhang H, Hwang ST, Khanna C, Helman LJ (2008) Inhibition of the CXCR4/CXCL12 chemokine pathway reduces the development of murine pulmonary metastases. Clin Exp Metastasis 25(3):201–211PubMedPubMedCentralCrossRef
Kim J, Yip ML, Shen X, Li H, Hsin LY, Labarge S, Heinrich EL, Lee W, Lu J, Vaidehi N (2012) Identification of anti-malarial compounds as novel antagonists to chemokine receptor CXCR4 in pancreatic cancer cells. PLoS ONE 7(2):e31004PubMedPubMedCentralCrossRef
Knolle PA, Gerken G (2000) Local control of the immune response in the liver. Immunol Rev 174:21–34PubMedCrossRef
Kobayashi N, Kubota K, Kato S, Watanabe S, Shimamura T, Kirikoshi H, Saito S, Ueda M, Endo I, Inayama Y, Maeda S, Nakajima A (2010) FOXP3+ regulatory T cells and tumoral indoleamine 2,3-dioxygenase expression predicts the carcinogenesis of intraductal papillary mucinous neoplasms of the pancreas. Pancreatology 10(5):631–640PubMedCrossRef
Koblish HK, Hansbury MJ, Bowman KJ, Yang G, Neilan CL, Haley PJ, Burn TC, Waeltz P, Sparks RB, Yue EW, Combs AP, Scherle PA, Vaddi K, Fridman JS (2010) Hydroxyamidine inhibitors of indoleamine-2,3-dioxygenase potently suppress systemic tryptophan catabolism and the growth of IDO-expressing tumors. Mol Cancer Ther 9(2):489–498PubMedCrossRef
Koshiba T, Hosotani R, Miyamoto Y, Ida J, Tsuji S, Nakajima S, Kawaguchi M, Kobayashi H, Doi R, Hori T, Fujii N, Imamura M (2000) Expression of stromal cell-derived factor 1 and CXCR4 ligand receptor system in pancreatic cancer: a possible role for tumor progression. Clin Cancer Res 6(9):3530–3535PubMed
Kowarik MC, Cepok S, Sellner J, Grummel V, Weber MS, Korn T, Berthele A, Hemmer B (2012) CXCL13 is the major determinant for B cell recruitment to the CSF during neuroinflammation. J Neuroinflammation 9:93PubMedPubMedCentralCrossRef
Krieg A, Riemer JC, Telan LA, Gabbert HE, Knoefel WT (2015) CXCR4-A Prognostic and clinicopathological biomarker for pancreatic ductal adenocarcinoma: a meta-analysis. PLoS One 10(6):e0130192PubMedPubMedCentralCrossRef
Kuniyasu H, Abbruzzese JL, Cleary KR, Fidler IJ (2001) Induction of ductal and stromal hyperplasia by basic fibroblast growth factor produced by human pancreatic carcinoma. Int J Oncol 19(4):681–685PubMed
Kurahara H, Shinchi H, Mataki Y, Maemura K, Noma H, Kubo F, Sakoda M, Ueno S, Natsugoe S, Takao S (2011) Significance of M2-polarized tumor-associated macrophage in pancreatic cancer. J Surg Res 167(2):e211–e219PubMedCrossRef
Lasky LA (1992) Selectins: interpreters of cell-specific carbohydrate information during inflammation. Science 258(5084):964–969PubMedCrossRef
Latchman Y, Wood CR, Chernova T, Chaudhary D, Borde M, Chernova I, Iwai Y, Long AJ, Brown JA, Nunes R, Greenfield EA, Bourque K, Boussiotis VA, Carter LL, Carreno BM, Malenkovich N, Nishimura H, Okazaki T, Honjo T, Sharpe AH, Freeman GJ (2001) PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol 2(3):261–268PubMedCrossRef
Lee Y, Kim SJ, Park HD, Park EH, Huang SM, Jeon SB, Kim JM, Lim DS, Koh SS (2010) PAUF functions in the metastasis of human pancreatic cancer cells and upregulates CXCR4 expression. Oncogene 29(1):56–67PubMedCrossRef
Legler DF, Loetscher M, Roos RS, Clark-Lewis I, Baggiolini M, Moser B (1998) B cell-attracting chemokine 1, a human CXC chemokine expressed in lymphoid tissues, selectively attracts B lymphocytes via BLR1/CXCR5. J Exp Med 187(4):655–660PubMedPubMedCentralCrossRef
Lekstan A, Lampe P, Lewin-Kowalik J, Olakowski M, Jablonska B, Labuzek K, Jedrzejowska-Szypulka H, Olakowska E, Gorka D, Filip I, Dranka-Bojarowska D (2012) Concentrations and activities of metalloproteinases 2 and 9 and their inhibitors (TIMPS) in chronic pancreatitis and pancreatic adenocarcinoma. J Physiol Pharmacol 63(6):589–599PubMed
Lepisto AJ, Moser AJ, Zeh H, Lee K, Bartlett D, McKolanis JR, Geller BA, Schmotzer A, Potter DP, Whiteside T, Finn OJ, Ramanathan RK (2008) A phase I/II study of a MUC1 peptide pulsed autologous dendritic cell vaccine as adjuvant therapy in patients with resected pancreatic and biliary tumors. Cancer Ther 6(B):955–964PubMedPubMedCentral
Li D, Wang H, Xiang JJ, Deng N, Wang PP, Kang YL, Tao J, Xu M (2010) Monoclonal antibodies targeting basic fibroblast growth factor inhibit the growth of B16 melanoma in vivo and in vitro. Oncol Rep 24(2):457–463PubMed
Li Q, Gao S, Yu Y, Wang W, Chen X, Wang R, Li T, Wang C, Li X, Wu X (2012) A novel bFGF antagonist peptide inhibits breast cancer cell growth. Mol Med Rep 6(1):210–214PubMed
Liang Z, Zhan W, Zhu A, Yoon Y, Lin S, Sasaki M, Klapproth JM, Yang H, Grossniklaus HE, Xu J, Rojas M, Voll RJ, Goodman MM, Arrendale RF, Liu J, Yun CC, Snyder JP, Liotta DC, Shim H (2012) Development of a unique small molecule modulator of CXCR4. PLoS ONE 7(4):e34038PubMedPubMedCentralCrossRef
Lim JY, Lee SE, Park G, Choi EY, Min CK (2014) Inhibition of indoleamine 2,3-dioxygenase by stereoisomers of 1-methyl tryptophan in an experimental graft-versus-tumor model. Exp Hematol 42(10):862-866.e3CrossRef
Lin N, Chen Z, Lu Y, Li Y, Hu K, Xu R (2014) Role of activated hepatic stellate cells in proliferation and metastasis of hepatocellular carcinoma. Hepatol Res 45(3):326–336PubMedCrossRef
Ling X, Spaeth E, Chen Y, Shi Y, Zhang W, Schober W, Hail N Jr, Konopleva M, Andreeff M (2013) The CXCR4 antagonist AMD3465 regulates oncogenic signaling and invasiveness in vitro and prevents breast cancer growth and metastasis in vivo. PLoS ONE 8(3):e58426PubMedPubMedCentralCrossRef
Liu X, Shin N, Koblish HK, Yang G, Wang Q, Wang K, Leffet L, Hansbury MJ, Thomas B, Rupar M, Waeltz P, Bowman KJ, Polam P, Sparks RB, Yue EW, Li Y, Wynn R, Fridman JS, Burn TC, Combs AP, Newton RC, Scherle PA (2010) Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity. Blood 115(17):3520–3530PubMedCrossRef
Liu C, Billadeau DD, Abdelhakim H, Leof E, Kaibuchi K, Bernabeu C, Bloom GS, Yang L, Boardman L, Shah VH, Kang N (2013) IQGAP1 suppresses TβRII-mediated myofibroblastic activation and metastatic growth in liver. J Clin Invest 123(3):1138–1156PubMedPubMedCentralCrossRef
Liyanage UK, Goedegebuure PS, Moore TT, Viehl CT, Moo-Young TA, Larson JW, Frey DM, Ehlers JP, Eberlein TJ, Linehan DC (2006) Increased prevalence of regulatory T cells (Treg) is induced by pancreas adenocarcinoma. J Immunother 29(4):416–424PubMedCrossRef
Loos M, Giese NA, Kleeff J, Giese T, Gaida MM, Bergmann F, Laschinger M, Büchler MW, Friess H (2008) Clinical significance and regulation of the costimulatory molecule B7-H1 in pancreatic cancer. Cancer Let 268(1):98–109CrossRef
Lui GY, Kovacevic Z, Menezes SV, Kalinowski DS, Merlot AM, Sahni S, Richardson DR (2015) Novel thiosemicarbazones regulate the signal transducer and activator of transcription 3 (STAT3) pathway: inhibition of constitutive and interleukin 6-induced activation by iron depletion. Mol Pharmacol 87(3):543–560PubMedCrossRef
Luker KE, Lewin SA, Mihalko LA, Schmidt BT, Winkler JS, Coggins NL, Thomas DG, Luker GD (2012) Scavenging of CXCL12 by CXCR7 promotes tumor growth and metastasis of CXCR4-positive breast cancer cells. Oncogene 31(45):4750–4758PubMedPubMedCentralCrossRef
Luo W, Yu Y, Wang R, He D, Wang C, Zeng X, Chen X, Tan X, Huang T, Wu X (2014) P7 peptides targeting bFGF sensitize colorectal cancer cells to CPT-11. Int J Mol Med 33(1):194–200PubMed
Luttrell LM, Roudabush FL, Choy EW, Miller WE, Field ME, Pierce KL, Lefkowitz RJ (2001) Activation and targeting of extracellular signal-regulated kinases by beta-arrestin scaffolds. Proc Natl Acad Sci U S A 98(5):2449–2454PubMedPubMedCentralCrossRef
Lutz MP, Esser IB, Flossmann-Kast BB, Vogelmann R, Lührs H, Friess H, Büchler MW, Adler G (1998) Overexpression and activation of the tyrosine kinase Src in human pancreatic carcinoma. Biochem Biophys Res Commun 243(2):503–508PubMedCrossRef
Ma WF, Du J, Fu LP, Fang R, Chen HY, Cai SH (2009) Phenotypic knockout of CXCR4 by a novel recombinant protein TAT/54R/KDEL inhibits tumors metastasis. Mol Cancer Res 7(10):1613–1621PubMedCrossRef
MacDonald IC, Schmidt EE, Morris VL, Chambers AF, Groom AC (1992) Intravital videomicroscopy of the chorioallantoic microcirculation: a model system for studying metastasis. Microvasc Res 44(2):185–199PubMedCrossRef
Maehara N, Matsumoto K, Kuba K, Mizumoto K, Tanaka M, Nakamura T (2001) NK4, a four-kringle antagonist of HGF, inhibits spreading and invasion of human pancreatic cancer cells. Br J Cancer 84(6):864–873PubMedPubMedCentralCrossRef
Maehara N, Nagai E, Mizumoto K, Sato N, Matsumoto K, Nakamura T, Narumi K, Nukiwa T, Tanaka M (2002) Gene transduction of NK4, HGF antagonist, inhibits in vitro invasion and in vivo growth of human pancreatic cancer. Clin Exp Metastasis 19(5):417–426PubMedCrossRef
Majuri ML, Mattila P, Renkonen R (1992) Recombinant E-selectin-protein mediates tumor cell adhesion via sialyl-Le(a) and sialyl-Le(x). Biochem Biophys Res Commun 182(3):1376–1382PubMedCrossRef
Makrilia N, Kollias A, Manolopoulos L, Syrigos K (2009) Cell adhesion molecules: role and clinical significance in cancer. Cancer Invest 27(10):1023–1037PubMedCrossRef
Mamelak AN, Jacoby DB (2007) Targeted delivery of antitumoral therapy to glioma and other malignancies with synthetic chlorotoxin (TM-601). Expert Opin Drug Deliv 4(2):175–186PubMedCrossRef
Mantovani A, Romero P, Palucka AK, Marincola FM (2008) Tumor immunity: effector response to tumor and role of the microenvironment. Lancet 371(9614):771–783PubMedCrossRef
Mao C, Domenico DR, Kim K, Hanson DJ, Howard JM (1995) Observations on the developmental patterns and the consequences of pancreatic exocrine adenocarcinoma: findings of 154 autopsies. Arch Surg 130(2):125–134PubMedCrossRef
Marchesi F, Monti P, Leone BE, Zerbi A, Vecchi A, Piemonti L, Mantovani A, Allavena P (2004) Increased survival, proliferation, and migration in metastatic human pancreatic tumor cells expressing functional CXCR4. Cancer Res 64(22):8420–8427PubMedCrossRef
Marchesi F, Piemonti L, Fedele G, Destro A, Roncalli M, Albarello L, Doglioni C, Anselmo A, Doni A, Bianchi P, Laghi L, Malesci A, Cervo L, Malosio M, Reni M, Zerbi A, Di Carlo V, Mantovani A, Allavena P (2008) The chemokine receptor CX3CR1 is involved in the neural tropism and malignant behavior of pancreatic ductal adenocarcinoma. Cancer Res 68(21):9060–9069PubMedCrossRef
Marcos-Ramiro B, García-Weber D, Millán J (2014) TNF-induced endothelial barrier disruption: beyond actin and Rho. Thromb Haemost 112(6):1088–1102PubMedCrossRef
McDonald PH, Chow CW, Miller WE, Laporte SA, Field ME, Lin FT, Davis RJ, Lefkowitz RJ (2000) Beta-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3. Science 290(5496):1574–1577PubMedCrossRef
Medina-Echeverz J, Fioravanti J, Díaz-Valdés N, Frank K, Aranda F, Gomar C, Ardaiz N, Dotor J, Umansky V, Prieto J, Berraondo P (2014) Harnessing high density lipoproteins to block transforming growth factor beta and to inhibit the growth of liver tumor metastases. PLoS ONE 9(5):e96799PubMedPubMedCentralCrossRef
Meijer J, Zeelenberg IS, Sipos B, Roos E (2006) The CXCR5 chemokine receptor is expressed by carcinoma cells and promotes growth of colon carcinoma in the liver. Cancer Res 66(19):9576–9582PubMedCrossRef
Metz R, Duhadaway JB, Rust S, Munn DH, Muller AJ, Mautino M, Prendergast GC (2010) Zinc protoporphyrin IX stimulates tumor immunity by disrupting the immunosuppressive enzyme indoleamine 2,3-dioxygenase. Mol Cancer Ther 9(6):1864–1871PubMedPubMedCentralCrossRef
Monti P, Leone BE, Marchesi F, Balzano G, Zerbi A, Scaltrini F, Pasquali C, Calori G, Pessi F, Sperti C, Di Carlo V, Allavena P, Piemonti L (2003) The CC chemokine MCP-1/CCL2 in pancreatic cancer progression: regulation of expression and potential mechanisms of antimalignant activity. Cancer Res 63(21):7451–7461PubMed
Moo-Young TA, Larson JW, Belt BA, Tan MC, Hawkins WG, Eberlein TJ, Goedegebuure PS, Linehan DC (2009) Tumor-derived TGF-beta mediates conversion of CD4+ Foxp3+ regulatory T cells in a murine model of pancreas cancer. J Immunother 32(1):12–21PubMedCrossRef
Moretti S, Menicali E, Voce P, Morelli S, Cantarelli S, Sponziello M, Colella R, Fallarino F, Orabona C, Alunno A, de Biase D, Bini V, Mameli MG, Filetti S, Gerli R, Macchiarulo A, Melillo RM, Tallini G, Santoro M, Puccetti P, Avenia N, Puxeddu E (2014) Indoleamine 2,3-dioxygenase 1 (IDO1) is up-regulated in thyroid carcinoma and drives the development of an immunosuppressant tumor microenvironment. J Clin Endocrinol Metab 99(5):E832–E840PubMedCrossRef
Mori T, Doi R, Koizumi M, Toyoda E, Ito D, Kami K, Masui T, Fujimoto K, Tamamura H, Hiramatsu K, Fujii N, Imamura M (2004a) CXCR4 antagonist inhibits stromal cell-derived factor 1-induced migration and invasion of human pancreatic cancer. Mol Cancer Ther 3(1):29–37PubMed
Mori T, Doi R, Koizumi M, Toyoda E, Ito D, Kami K, Masui T, Fujimoto K, Tamamura H, Hiramatsu K, Fujii N, Imamura M (2004b) CXCR4 antagonist inhibits stromal cell-derived factor 1-induced migration and invasion of human pancreatic cancer. Mol Cancer Ther 3(1):29–37PubMed
Muller AJ, DuHadaway JB, Donover PS, Sutanto-Ward E, Prendergast GC (2005) Inhibition of indoleamine 2,3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy. Nat Med 11(3):312–319PubMedCrossRef
Muller AJ, DuHadaway JB, Jaller D, Curtis P, Metz R, Prendergast GC (2010) Immunotherapeutic suppression of indoleamine 2,3-dioxygenase and tumor growth with ethyl pyruvate. Cancer Res 70(5):1845–1853PubMedPubMedCentralCrossRef
Nagakawa Y, Aoki T, Kasuya K, Tsuchida A, Koyanagi Y (2002) Histologic features of venous invasion, expression of vascular endothelial growth factor and matrix metalloproteinase-2 and matrix metalloproteinase-9, and the relation with liver metastasis in pancreatic cancer. Pancreas 24(2):169–178PubMedCrossRef
Nakahashi C, Oda T, Kinoshita T, Ueda T, Konishi M, Nakagohri T, Inoue K, Furuse J, Ochiai A, Ohkohchi N (2003) The impact of liver metastasis on mortality in patients initially diagnosed with locally advanced or resectable pancreatic cancer. Int J Gastrointest Cancer 33(2–3):155–164PubMedCrossRef
Nakatani K, Kaneda K, Seki S, Nakajima Y (2004) Pit cells as liver-associated natural killer cells: morphology and function. Med Electron Microsc 37(1):29–36PubMedCrossRef
Naugler WE, Sakurai T, Kim S, Maeda S, Kim K, Elsharkawy AM, Karin M (2007) Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science 317(5834):121–124PubMedCrossRef
Nguyen DX, Massagué J (2007) Genetic determinants of cancer metastasis. Nat Rev Genet 8(5):341–352PubMedCrossRef
Nozawa H, Chiu C, Hanahan D (2006) Infiltrating neutrophils mediate the initial angiogenic switch in a mouse model of multistage carcinogenesis. Proc Natl Acad Sci U S A 103(33):12493–12498PubMedPubMedCentralCrossRef
Nummer D, Suri-Payer E, Schmitz-Winnenthal H, Bonertz A, Galindo L, Antolovich D, Koch M, Büchler M, Weitz J, Schirrmacher V, Beckhove P (2007) Role of tumor endothelium in CD4+ CD25+ regulatory T cell infiltration of human pancreatic carcinoma. J Natl Cancer Inst 99(15):1188–1199PubMedCrossRef
Oettle H et al (2012) Final results of a phase I/II study in patients with pancreatic cancer, malignant melanoma, and colorectal carcinoma with trabedersen. J Clin Oncol 30:4034
Okamoto A, Nikaido T, Ochiai K, Takakura S, Saito M, Aoki Y, Ishii N, Yanaihara N, Yamada K, Takikawa O, Kawaguchi R, Isonishi S, Tanaka T, Urashima M (2005) Indoleamine 2,3-dioxygenase serves as a marker of poor prognosis in gene expression profiles of serous ovarian cancer cells. Clin Cancer Res 11(16):6030–6039PubMedCrossRef
Okazaki T, Maeda A, Nishimura H, Kurosaki T, Honjo T (2001) PD-1 immunoreceptor inhibits B cell receptor-mediated signaling by recruiting src homology 2-domain-containing tyrosine phosphatase 2 to phosphotyrosine. Proc Natl Acad Sci U S A 98(24):13866–13871PubMedPubMedCentralCrossRef
Okudaira K, Hokari R, Tsuzuki Y, Okada Y, Komoto S, Watanabe C, Kurihara C, Kawaguchi A, Nagao S, Azuma M, Yagita H, Miura S (2009) Blockade of B7-H1 or B7-DC induces an anti-tumor effect in a mouse pancreatic cancer model. Int J Oncol 35(4):741–749PubMed
Olaso E, Salado C, Egilegor E, Gutierrez V, Santisteban A, Sancho-Bru P, Friedman SL, Vidal-Vanaclocha F (2003) Proangiogenic role of tumor-activated hepatic stellate cells in experimental melanoma metastasis. Hepatology 37(3):674–685PubMedCrossRef
Opitz CA, Litzenburger UM, Opitz U, Sahm F, Ochs K, Lutz C, Wick W, Platten M (2011) The indoleamine-2,3-dioxygenase (IDO) inhibitor 1-methyl-d-tryptophan upregulates IDO1 in human cancer cells. PLoS ONE 6(5):e19823PubMedPubMedCentralCrossRef
Orr FW, Wang HH (2001) Tumor cell interactions with the microvasculature: a rate-limiting step in metastasis. Surg Oncol Clin N Am 10(2):357–381PubMed
Paget S (1889) The distribution of secondary growth in cancer of the breast. Lancet 1:571–573CrossRef
Palumbo JS, Talmage KE, Massari JV, La Jeunesse CM, Flick MJ, Kombrinck KW, Jirousková M, Degen JL (2005) Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells. Blood 105(1):178–185PubMedCrossRef
Paschos KA, Majeed AW, Bird NC (2014) Natural history of hepatic metastases from colorectal cancer–pathobiological pathways with clinical significance. World J Gastroenterol 20(14):3719–3737PubMedPubMedCentralCrossRef
Peng YP, Zhu Y, Zhang JJ, Xu ZK, Qian ZY, Dai CC, Jiang KR, Wu JL, Gao WT, Li Q, Du Q, Miao Y (2013) Comprehensive analysis of the percentage of surface receptors and cytotoxic granules positive natural killer cells in patients with pancreatic cancer, gastric cancer, and colorectal cancer. J Transl Med 11:262PubMedPubMedCentralCrossRef
Percherancier Y, Berchiche YA, Slight I, Volkmer-Engert R, Tamamura H, Fujii N, Bouvier M, Heveker N (2005) Bioluminescence resonance energy transfer reveals ligand-induced conformational changes in CXCR4 homo- and heterodimers. J Biol Chem 280(11):9895–9903PubMedCrossRef
Pereira JP, Kelly LM, Cyster JG (2010) Finding the right niche: b-cell migration in the early phases of T-dependent antibody responses. Int Immunol 22(6):413–419PubMedPubMedCentralCrossRef
Pertovaara L, Sistonen L, Bos TJ, Vogt PK, Keski-Oja J, Alitalo K (1989) Enhanced jun gene expression is an early genomic response to transforming growth factor beta stimulation. Mol Cell Biol 9(3):1255–1262PubMedPubMedCentralCrossRef
Pevzner V, Wolf I, Burgstahler R, Förster R, Lipp M (1999) Regulation of expression of chemokine receptor BLR1/CXCR5 during B cell maturation. Curr Top Microbiol Immunol 246:79–84PubMed
Publicover J, Gaggar A, Nishimura S, Van Horn CM, Goodsell A, Muench MO, Reinhardt RL, van Rooijen N, Wakil AE, Peters M, Cyster JG, Erle DJ, Rosenthal P, Cooper S, Baron JL (2013) Age-dependent hepatic lymphoid organization directs successful immunity to hepatitis B. J Clin Invest 123(9):3728–3739PubMedPubMedCentralCrossRef
Qi C, Li B, Guo S, Wei B, Shao C, Li J, Yang Y, Zhang Q, Li J, He X, Wang L, Zhang Y (2015) P-Selectin-Mediated Adhesion between Platelets and Tumor Cells Promotes Intestinal Tumorigenesis in Apc(Min/+) Mice. Int J Biol Sci 11(6):679–687PubMedPubMedCentralCrossRef
Rajagopal S, Kim J, Ahn S, Craig S, Lam CM, Gerard NP, Gerard C, Lefkowitz RJ (2010a) Beta-arrestin- but not G protein-mediated signaling by the “decoy” receptor CXCR7. Proc Natl Acad Sci U S A 107(2):628–632PubMedPubMedCentralCrossRef
Rajagopal S, Rajagopal K, Lefkowitz RJ (2010b) Teaching old receptors new tricks: biasing seven-transmembrane receptors. Nat Rev Drug Discov 9(5):373–386PubMedPubMedCentralCrossRef
Ramanathan RK, Lee KM, McKolanis J, Hitbold E, Schraut W, Moser AJ, Warnick E, Whiteside T, Osborne J, Kim H, Day R, Troetschel M, Finn OJ (2005) Phase I study of a MUC1 vaccine composed of different doses of MUC1 peptide with SB-AS2 adjuvant in resected and locally advanced pancreatic cancer. Cancer Immunol Immunother 54(3):254–264PubMedCrossRef
Rammensee HG, Falk K, Rötzschke O (1993) Peptides naturally presented by MHC class I molecules. Annu Rev Immunol 11:213–244PubMedCrossRef
Rapraeger AC, Krufka A, Olwin BB (1991) Requirement of heparan sulfate for bFGF-mediated fibroblast growth and myoblast differentiation. Science 252(5013):1705–1708PubMedCrossRef
Ray P, Lewin SA, Mihalko LA, Lesher-Perez SC, Takayama S, Luker KE, Luker GD (2012) Secreted CXCL12 (SDF-1) forms dimers under physiological conditions. Biochem J 442(2):433–442PubMedPubMedCentralCrossRef
Razis E, Kalogeras KT, Kotoula V, Eleftheraki AG, Nikitas N, Kronenwett R, Timotheadou E, Christodoulou C, Pectasides D, Gogas H, Wirtz RM, Makatsoris T, Bafaloukos D, Aravantinos G, Televantou D, Pavlidis N, Fountzilas G (2012) Improved outcome of high-risk early HER2 positive breast cancer with high CXCL13-CXCR5 messenger RNA expression. Clin Breast Cancer 12(3):183–193PubMedCrossRef
Rodríguez PC, Ochoa AC (2008) Arginine regulation by myeloid derived suppressor cells and tolerance in cancer: mechanisms and therapeutic perspectives. Immunol Rev 222:180–191PubMedPubMedCentralCrossRef
Rodriguez PC, Quiceno DG, Zabaleta J, Ortiz B, Zea AH, Piazuelo MB, Delgado A, Correa P, Brayer J, Sotomayor EM, Antonia S, Ochoa JB, Ochoa AC (2004) Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses. Cancer Res 64(16):5839–5849PubMedCrossRef
Roland CL, Dineen SP, Toombs JE, Carbon JG, Smith CW, Brekken RA, Barnett CC Jr (2010) Tumor-derived intercellular adhesion molecule-1 mediates tumor-associated leukocyte infiltration in orthotopic pancreatic xenografts. Exp Biol Med (Maywood) 235(2):263–270CrossRef
Romain B, Hachet-Haas M, Rohr S, Brigand C, Galzi JL, Gaub MP, Pencreach E, Guenot D (2014) Hypoxia differentially regulated CXCR4 and CXCR7 signaling in colon cancer. Mol Cancer 13:58PubMedPubMedCentralCrossRef
Rosenbaum J, Blazejewski S, Préaux AM, Mallat A, Dhumeaux D, Mavier P (1995) Fibroblast growth factor 2 and transforming growth factor beta 1 interactions in human liver myofibroblasts. Gastroenterology 109(6):1986–1996PubMedCrossRef
Rossi JF, Négrier S, James ND, Kocak I, Hawkins R, Davis H, Prabhakar U, Qin X, Mulders P, Berns B (2010) A phase I/II study of siltuximab (CNTO 328), an anti-interleukin-6 monoclonal antibody, in metastatic renal cell cancer. Br J Cancer 103(8):1154–1162PubMedPubMedCentralCrossRef
Ryschich E, Nötzel T, Hinz U, Autschbach F, Ferguson J, Simon I, Weitz J, Fröhlich B, Klar E, Büchler MW, Schmidt J (2005) Control of T-cell-mediated immune response by HLA class I in human pancreatic carcinoma. Clin Cancer Res 11(2 Pt 1):498–504PubMed
Sadanandam A, Varney ML, Singh RK (2008) Identification of semaphorin 5A interacting protein by applying apriori knowledge and peptide complementarity related to protein evolution and structure. Genomics Proteomics Bioinformatics 6(3–4):163–174PubMedCrossRef
Sadanandam A, Sidhu SS, Wullschleger S, Singh S, Varney ML, Yang CS, Ashour AE, Batra SK, Singh RK (2012) Secreted semaphorin 5A suppressed pancreatic tumor burden but increased metastasis and endothelial cell proliferation. Br J Cancer 107(3):501–507PubMedPubMedCentralCrossRef
Saito T, Tomida M (2005) Generation of inhibitory DNA aptamers against human hepatocyte growth factor. DNA Cell Biol 24(10):624–633PubMedCrossRef
Sakaguchi S (2004) Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 22:531–562PubMedCrossRef
Sakamoto K, Haga Y, Yoshimura R, Egami H, Yokoyama Y, Akagi M (1987) Comparative effectiveness of the tumor diagnostics, CA 19-9, CA 125 and carcinoembryonic antigen in patients with diseases of the digestive system. Gut 28(3):323–329PubMedPubMedCentralCrossRef
Sanford DE, Belt BA, Panni RZ, Mayer A, Deshpande AD, Carpenter D, Mitchem JB, Plambeck-Suess SM, Worley LA, Goetz BD, Wang-Gillam A, Eberlein TJ, Denardo DG, Goedegebuure SP, Linehan DC (2013) Inflammatory monocyte mobilization decreases patient survival in pancreatic cancer: a role for targeting the CCL2/CCR2 axis. Clin Cancer Res 19(13):3404–3415PubMedPubMedCentralCrossRef
Santiago B, Gutierrez-Cañas I, Dotor J, Palao G, Lasarte JJ, Ruiz J, Prieto J, Borrás-Cuesta F, Pablos JL (2005) Topical application of a peptide inhibitor of transforming growth factor-beta1 ameliorates bleomycin-induced skin fibrosis. J Invest Dermatol 125(3):450–455PubMedCrossRef
Schlingensiepen KH, Jaschinski F, Lang SA, Moser C, Geissler EK, Schlitt HJ, Kielmanowicz M, Schneider A (2011) Transforming growth factor-beta 2 gene silencing with trabedersen (AP 12009) in pancreatic cancer. Cancer Sci 102(6):1193–1200PubMedCrossRef
Scholz A, Heinze S, Detjen KM, Peters M, Welzel M, Hauff P, Schirner M, Wiedenmann B, Rosewicz S (2003) Activated signal transducer and activator of transcription 3 (STAT3) supports the malignant phenotype of human pancreatic cancer. Gastroenterology 125(3):891–905PubMedCrossRef
Schumacher D, Strilic B, Sivaraj KK, Wettschureck N, Offermanns S (2013) Platelet-derived nucleotides promote tumor-cell transendothelial migration and metastasis via P2Y2 receptor. Cancer Cell 24(1):130–137PubMedCrossRef
Seki S, Habu Y, Kawamura T, Takeda K, Dobashi H, Ohkawa T, Hiraide H (2000) The liver as a crucial organ in the first line of host defense: the roles of Kupffer cells, natural killer (NK) cells and NK1.1 Ag+ T cells in T helper 1 immune responses. Immunol Rev 174:35–46PubMedCrossRef
Shen B, Zheng MQ, Lu JW, Jiang Q, Wang TH, Huang XE (2013) CXCL12-CXCR4 promotes proliferation and invasion of pancreatic cancer cells. Asian Pac J Cancer Prev 14(9):5403–5408PubMedCrossRef
Shi Q, Le X, Abbruzzese JL, Peng Z, Qian CN, Tang H, Xiong Q, Wang B, Li XC, Xie K (2001) Constitutive Sp1 activity is essential for differential constitutive expression of vascular endothelial growth factor in human pancreatic adenocarcinoma. Cancer Res 61(10):4143–4154PubMed
Shi WD, Meng ZQ, Chen Z, Lin JH, Zhou ZH, Liu LM (2009) Identification of liver metastasis-related genes in a novel human pancreatic carcinoma cell model by microarray analysis. Cancer Lett 283(1):84–91PubMedCrossRef
Shi C, Washington MK, Chaturvedi R, Drosos Y, Revetta FL, Weaver CJ, Buzhardt E, Yull FE, Blackwell TS, Sosa-Pineda B, Whitehead RH, Beauchamp RD, Wilson KT, Means AL (2014a) Fibrogenesis in pancreatic cancer is a dynamic process regulated by macrophage-stellate cell interaction. Lab Invest 94(4):409–421PubMedPubMedCentralCrossRef
Shi W, Meng Z, Chen Z, Hua Y, Gao H, Wang P, Lin J, Zhou Z, Luo J, Liu L (2014b) RNA interference against MDM2 suppresses tumor growth and metastasis in pancreatic carcinoma SW1990HM cells. Mol Cell Biochem 387(1–2):1–8PubMedCrossRef
Shinriki S, Jono H, Ota K, Ueda M, Kudo M, Ota T, Oike Y, Endo M, Ibusuki M, Hiraki A, Nakayama H, Yoshitake Y, Shinohara M, Ando Y (2009) Humanized anti-interleukin-6 receptor antibody suppresses tumor angiogenesis and in vivo growth of human oral squamous cell carcinoma. Clin Cancer Res 15(17):5426–5434PubMedCrossRef
Shinriki S, Jono H, Ueda M, Ota K, Ota T, Sueyoshi T, Oike Y, Ibusuki M, Hiraki A, Nakayama H, Shinohara M, Ando Y (2011) Interleukin-6 signalling regulates vascular endothelial growth factor-C synthesis and lymphangiogenesis in humanoral squamous cell carcinoma. J Pathol 225(1):142–150PubMedCrossRef
Sica A, Schioppa T, Mantovani A, Allavena P (2006) Tumor-associated macrophages are a distinct M2 polarised population promoting tumor progression: potential targets of anti-cancer therapy. Eur J Cancer 42(6):717–727PubMedCrossRef
Singh S, Srivastava SK, Bhardwaj A, Owen LB, Singh AP (2010) CXCL12-CXCR4 signalling axis confers gemcitabine resistance to pancreatic cancer cells: a novel target for therapy. Br J Cancer 103(11):1671–1679PubMedPubMedCentralCrossRef
Sohn TA, Yeo CJ, Cameron JL, Koniaris L, Kaushal S, Abrams RA, Sauter PK, Coleman J, Hruban RH, Lillemoe KD (2000) Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg 4(6):567–579PubMedCrossRef
Stathis A, Moore MJ (2010) Advanced pancreatic carcinoma: current treatment and future challenges. Nat Rev Clin Oncol 7(3):163–172PubMedCrossRef
Stegner D, Dütting S, Nieswandt B (2014) Mechanistic explanation for platelet contribution to cancer metastasis. Thromb Res 133(Suppl 2):S149–S157PubMedCrossRef
Steinman RM, Hawiger D, Nussenzweig MC (2003) Tolerogenic dendritic cells. Annu Rev Immunol 21:685–711PubMedCrossRef
Stenner F, Liewen H, Göttig S, Henschler R, Markuly N, Kleber S, Faust M, Mischo A, Bauer S, Zweifel M, Knuth A, Renner C, Wadle A (2013) RP1 is a phosphorylation target of CK2 and is involved in cell adhesion. PLoS ONE 8(7):e67595PubMedPubMedCentralCrossRef
Stephens LA, Gray D, Anderton SM (2005) CD4+ CD25+ regulatory T cells limit the risk of autoimmune disease arising from T cell receptor crossreactivity. Proc Natl Acad Sci U S A 102(48):17418–17423PubMedPubMedCentralCrossRef
Suciu-Foca N, Feirt N, Zhang QY, Vlad G, Liu Z, Lin H, Chang CC, Ho EK, Colovai AI, Kaufman H, D’Agati VD, Thaker HM, Remotti H, Galluzzo S, Cinti P, Rabitti C, Allendorf J, Chabot J, Caricato M, Coppola R, Berloco P, Cortesini R (2007) Soluble Ig-like transcript 3 inhibits tumor allograft rejection in humanized SCID mice and T cell responses in cancer patients. J Immunol 178(11):7432–7441PubMedCrossRef
Sudha T, Phillips P, Kanaan C, Linhardt RJ, Borsig L, Mousa SA (2012) Inhibitory effect of non-anticoagulant heparin (S-NACH) on pancreatic cancer cell adhesion and metastasis in human umbilical cord vessel segment and in mouse model. Clin Exp Metastasis 29(5):431–439PubMedCrossRef
Sung B, Jhurani S, Ahn KS, Mastuo Y, Yi T, Guha S, Liu M, Aggarwal BB (2008) Zerumbone down-regulates chemokine receptor CXCR4 expression leading to inhibition of CXCL12-induced invasion of breast and pancreatic tumor cells. Cancer Res 68(21):8938–8944PubMedCrossRef
Takada A, Ohmori K, Takahashi N, Tsuyuoka K, Yago A, Zenita K, Hasegawa A, Kannagi R (1991) Adhesion of human cancer cells to vascular endothelium mediated by a carbohydrate antigen, sialyl Lewis A. Biochem Biophys Res Commun 179(2):713–719PubMedCrossRef
Takada A, Ohmori K, Yoneda T, Tsuyuoka K, Hasegawa A, Kiso M, Kannagi R (1993) Contribution of carbohydrate antigens sialyl Lewis A and sialyl Lewis X to adhesion of human cancer cells to vascular endothelium. Cancer Res 53(2):354–361PubMed
Takahashi T, Tagami T, Yamazaki S, Uede T, Shimizu J, Sakaguchi N, Mak TW, Sakaguchi S (2000) Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J Exp Med 192(2):303–310PubMedPubMedCentralCrossRef
Tamamura H, Omagari A, Hiramatsu K, Gotoh K, Kanamoto T, Xu Y, Kodama E, Matsuoka M, Hattori T, Yamamoto N, Nakashima H, Otaka A, Fujii N (2001) Development of specific CXCR4 inhibitors possessing high selectivity indexes as well as complete stability in serum based on an anti-HIV peptide T140. Bioorg Med Chem Lett 11(14):1897–1902PubMedCrossRef
Tamamura H, Tsutsumi H, Masuno H, Fujii N (2007) Development of low molecular weight CXCR4 antagonists by exploratory structural tuning of cyclic tetra- and pentapeptide-scaffolds towards the treatment of HIV infection, cancer metastasis and rheumatoid arthritis. Curr Med Chem 14(1):93–102PubMedCrossRef
Tan MC, Goedegebuure PS, Belt BA, Flaherty B, Sankpal N, Gillanders WE, Eberlein TJ, Hsieh CS, Linehan DC (2009) Disruption of CCR5-dependent homing of regulatory T cells inhibits tumor growth in a murine model of pancreatic cancer. J Immunol 182(3):1746–17455PubMedPubMedCentralCrossRef
Tao J, Xiang JJ, Li D, Deng N, Wang H, Gong YP (2010) Selection and characterization of a human neutralizing antibody to human fibroblast growth factor-2. Biochem Biophys Res Commun 394(3):767–773PubMedCrossRef
Tarp MA, Clausen H (2008) Mucin-type O-glycosylation and its potential use in drug and vaccine development. Biochim Biophys Acta 1780(3):546–563PubMedCrossRef
Ten Kate M, Hofland LJ, van Grevenstein WM, van Koetsveld PV, Jeekel J, van Eijck CH (2004) Influence of proinflammatory cytokines on the adhesion of human colon carcinoma cells to lung microvascular endothelium. Int J Cancer 112(6):943–950PubMedCrossRef
Ten Kate M, van der Wal JB, Sluiter W, Hofland LJ, Jeekel J, Sonneveld P, van Eijck CH (2006) The role of superoxide anions in the development of distant tumor recurrence. Br J Cancer 95(11):1497–1503PubMedPubMedCentralCrossRef
Ten Kate M, Aalbers AG, Sluiter W, Hofland LJ, Sonneveld P, Jeekel J, Van Eijck CH (2007) Polymorphonuclear leukocytes increase the adhesion of circulating tumor cells to microvascular endothelium. Anticancer Res 27(1A):17–22PubMed
Teraoka H, Sawada T, Nishihara T, Yashiro M, Ohira M, Ishikawa T, Nishino H, Hirakawa K (2001) Enhanced VEGF production and decreased immunogenicity induced by TGF-beta 1 promote liver metastasis of pancreatic cancer. Br J Cancer 85(4):612–617PubMedPubMedCentralCrossRef
Théret N, Musso O, Campion JP, Turlin B, Loréal O, L’Helgoualc’h A, Clément B (1997) Overexpression of matrix metalloproteinase-2 and tissue inhibitor of matrix metalloproteinase-2 in liver from patients with gastrointestinal adenocarcinoma and no detectable metastasis. Int J Cancer 74(4):426–432PubMedCrossRef
Thornton AM, Shevach EM (2000) Suppressor effector function of CD4+ CD25+ immunoregulatory T cells is antigen nonspecific. J Immunol 164(1):183–190PubMedCrossRef
Tien YW, Wu YM, Lin WC, Lee HS, Lee PH (2009) Pancreatic carcinoma cells stimulate proliferation and matrix synthesis of hepatic stellate cells. J Hepatol 51(2):307–314PubMedCrossRef
Tímár J, Tóvári J, Rásó E, Mészáros L, Bereczky B, Lapis K (2005) Platelet-mimicry of cancer cells: epiphenomenon with clinical significance. Oncology 69(3):185–201PubMedCrossRef
Timmers M, Vekemans K, Vermijlen D, Asosingh K, Kuppen P, Bouwens L, Wisse E, Braet F (2004) Interactions between rat colon carcinoma cells and Kupffer cells during the onset of hepatic metastasis. Int J Cancer 112(5):793–802PubMedCrossRef
Tischer E, Mitchell R, Hartman T, Silva M, Gospodarowicz D, Fiddes JC, Abraham JA (1991) The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem 266(18):11947–11954PubMed
Tözeren A, Kleinman HK, Grant DS, Morales D, Mercurio AM, Byers SW (1995) E-selectin-mediated dynamic interactions of breast- and colon-cancer cells with endothelial-cell monolayers. Int J Cancer 60(3):426–431PubMedCrossRef
Tsuji F, Seki I, Aono H, Odani N, Mizutani K, Okamoto M, Sasano M (2007) Bucillamine mechanism inhibiting IL-1beta-induced VEGF production from fibroblast-like synoviocytes. Int Immunopharmacol 7(12):1569–1576PubMedCrossRef
Uotani H, Yamashita I, Nagata T, Kishimoto H, Kashii Y, Tsukada K (2001) Induction of E-selectin after partial hepatectomy promotes metastases to liver in mice. J Surg Res 96(2):197–203PubMedCrossRef
Vasilyeva ED, Kaledin V, Nikolin VP, Popova NA, Kirilyuk IA, Grigor’ev IA (2012) Accelerated rejection of the second transplants of immunogenic tumor in mice under inhibition of indoleamine 2,3-dioxygenase activity by ethyl pyruvate. Exp Oncol 34(1):66–68PubMed
Veldkamp CT, Peterson FC, Pelzek AJ, Volkman BF (2005) The monomer-dimer equilibrium of stromal cell-derived factor-1 (CXCL 12) is altered by pH, phosphate, sulfate, and heparin. Protein Sci 14(4):1071–1081PubMedPubMedCentralCrossRef
Venkatasubbarao K, Choudary A, Freeman JW (2005) Farnesyl transferase inhibitor (R115777)-induced inhibition of STAT3(Tyr705) phosphorylation in human pancreatic cancer cell lines require extracellular signal-regulated kinases. Cancer Res 65(7):2861–2871PubMedCrossRef
Voorhees PM, Chen Q, Kuhn DJ, Small GW, Hunsucker SA, Strader JS, Corringham RE, Zaki MH, Nemeth JA, Orlowski RZ (2007) Inhibition of interleukin-6 signaling with CNTO 328 enhances the activity of bortezomib in preclinical models of multiple myeloma. Clin Cancer Res 13(21):6469–6478PubMedCrossRef
Voorhees PM, Chen Q, Small GW, Kuhn DJ, Hunsucker SA, Nemeth JA, Orlowski RZ (2009) Targeted inhibition of interleukin-6 with CNTO 328 sensitizes pre-clinical models of multiple myeloma to dexamethasone-mediated cell death. Br J Haematol 145(4):481–490PubMedPubMedCentralCrossRef
Waghray M, Yalamanchili M, di Magliano MP, Simeone DM (2013) Deciphering the role of stroma in pancreatic cancer. Curr Opin Gastroenterol 29(5):537–543PubMedPubMedCentralCrossRef
Wang C, Lin S, Nie Y, Jia X, Wang J, Xiao J, Wu J, Li X, Wu X (2010) Mechanism of antitumor effect of a novel bFGF binding peptide on human colon cancer cells. Cancer Sci 101(5):1212–1218PubMedCrossRef
Wang L, Park H, Chhim S, Ding Y, Jiang W, Queen C, Kim KJ (2012) A novel monoclonal antibody to fibroblast growth factor 2 effectively inhibits growth of hepatocellular carcinoma xenografts. Mol Cancer Ther 11(4):864–872PubMedPubMedCentralCrossRef
Wang B, Wang W, Niu W, Liu E, Liu X, Wang J, Peng C, Liu S, Xu L, Wang L, Niu J (2014) SDF-1/CXCR4 axis promotes directional migration of colorectal cancer cells through upregulation of integrin αvβ6. Carcinogenesis 35(2):282–291PubMedCrossRef
Weekes CD, Song D, Arcaroli J, Wilson LA, Rubio-Viqueira B, Cusatis G, Garrett-Mayer E, Messersmith WA, Winn RA, Hidalgo M (2012) Stromal cell-derived factor 1α mediates resistance to mTOR-directed therapy in pancreatic cancer. Neoplasia 14(8):690–701PubMedPubMedCentralCrossRef
Wei D, Le X, Zheng L, Wang L, Frey JA, Gao AC, Peng Z, Huang S, Xiong HQ, Abbruzzese JL, Xie K (2003) Stat3 activation regulates the expression of vascular endothelial growth factor and human pancreatic cancer angiogenesis and metastasis. Oncogene 22(3):319–329PubMedCrossRef
Wei D, Wang L, He Y, Xiong HQ, Abbruzzese JL, Xie K (2004) Celecoxib inhibits vascular endothelial growth factor expression in and reduces angiogenesis and metastasis of human pancreatic cancer via suppression of Sp1 transcription factor activity. Cancer Res 64(6):2030–2038PubMedCrossRef
Weiss L, Orr FW, Honn KV (1988) Interactions of cancer cells with the microvasculature during metastasis. FASEB J 2(1):12–21PubMed
Witkiewicz A, Williams TK, Cozzitorto J, Durkan B, Showalter SL, Yeo CJ, Brody JR (2008) Expression of indoleamine 2,3-dioxygenase in metastatic pancreatic ductal adenocarcinoma recruits regulatory T cells to avoid immune detection. J Am Coll Surg 206(5):849–854PubMedCrossRef
Wu X, Yan Q, Huang Y, Huang H, Su Z, Xiao J, Zeng Y, Wang Y, Nie C, Yang Y, Li X (2010) Isolation of a novel basic FGF-binding peptide with potent antiangiogenetic activity. J Cell Mol Med 14(1–2):351–356PubMedPubMedCentralCrossRef
Wu J, Jiao Y, Dal Molin M, Maitra A, de Wilde RF, Wood LD, Eshleman JR, Goggins MG, Wolfgang CL, Canto MI, Schulick RD, Edil BH, Choti MA, Adsay V, Klimstra DS, Offerhaus GJ, Klein AP, Kopelovich L, Carter H, Karchin R, Allen PJ, Schmidt CM, Naito Y, Diaz LA Jr, Kinzler KW, Papadopoulos N, Hruban RH, Vogelstein B (2011) Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways. Proc Natl Acad Sci U S A 108(52):21188–21193PubMedPubMedCentralCrossRef
Wu X, Huang H, Wang C, Lin S, Huang Y, Wang Y, Liang G, Yan Q, Xiao J, Wu J, Yang Y, Li X (2013) Identification of a novel peptide that blocks basic fibroblast growth factor-mediated cell proliferation. Oncotarget 4(10):1819–1828PubMedPubMedCentralCrossRef
Xiong HQ, Abbruzzese JL, Lin E, Wang L, Zheng L, Xie K (2011) NF-kappaB activity blockade impairs the angiogenic potential of human pancreatic cancer cells. Int J Cancer 108(2):181–188CrossRef
Xu K, Gao H, Shu HK (2011) Celecoxib can induce vascular endothelial growth factor expression and tumor angiogenesis. Mol Cancer The 10(1):138–147CrossRef
Xu X, Wang Y, Chen J, Ma H, Shao Z, Chen H, Jin G (2012) High expression of CX3CL1/CX3CR1 axis predicts a poor prognosis of pancreatic ductal adenocarcinoma. J Gastrointest Surg 16(8):1493–1498PubMedCrossRef
Yachida S, Iacobuzio-Donahue CA (2009) The pathology and genetics of metastatic pancreatic cancer. Arch Pathol Lab Med 133:413–422PubMed
Yachida S, Iacobuzio-Donahue CA (2013) Evolution and dynamics of pancreatic cancer progression. Oncogene 32(45):5253–5260PubMedCrossRef
Yadav VR, Sung B, Prasad S, Kannappan R, Cho SG, Liu M, Chaturvedi MM, Aggarwal BB (2010) Celastrol suppresses invasion of colon and pancreatic cancer cells through the downregulation of expression of CXCR4 chemokine receptor. J Mol Med (Berl) 88(12):1243–1253CrossRef
Yamada S, Shimada M, Utsunomiya T, Morine Y, Imura S, Ikemoto T, Mori H, Arakawa Y, Kanamoto M, Iwahashi S, Saito Y (2014) CXC receptor 4 and stromal cell-derived factor 1 in primary tumors and liver metastases of colorectal cancer. J Surg Res 187(1):107–112PubMedCrossRef
Yamahira A, Narita M, Iwabuchi M, Uchiyama T, Iwaya S, Ohiwa R, Nishizawa Y, Suzuki T, Yokoyama Y, Hashimoto S, Takizawa J, Sone H, Takahashi M (2014) Activation of the leukemia plasmacytoid dendritic cell line PMDC05 by Toho-1, a novel IDO inhibitor. Anticancer Res 34(8):4021–4028PubMed
Yamamoto T, Yanagimoto H, Satoi S, Toyokawa H, Hirooka S, Yamaki S, Yui R, Yamao J, Kim S, Kwon AH (2012) Circulating CD4+ CD25+ regulatory T cells in patients with pancreatic cancer. Pancreas 41(3):409–415PubMedCrossRef
Yamauchi H, Kikuchi Y, Kakizaki K (1995) Relation between the stromal volume and liver metastasis in ductal cell carcinoma of the pancreas. Tohoku J Exp Med 177(2):179–181PubMedCrossRef
Yang Q, Zhang F, Ding Y, Huang J, Chen S, Wu Q, Wang Z, Wang Z, Chen C (2014) Antitumour activity of the recombination polypeptide GST-NT21MP is mediated by inhibition of CXCR4 pathway in breast cancer. Br J Cancer 110(5):1288–1297PubMedPubMedCentralCrossRef
Yayon A, Klagsbrun M, Esko JD, Leder P, Ornitz DM (1991) Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor. Cell 64(4):841–848PubMedCrossRef
Yezhelyev MV, Koehl G, Guba M, Brabletz T, Jauch KW, Ryan A, Barge A, Green T, Fennell M, Bruns CJ (2004) Inhibition of SRC tyrosine kinase as treatment for human pancreatic cancer growing orthotopically in nude mice. Clin Cancer Res 10(23):8028–8036PubMedCrossRef
Yoshidome H, Kohno H, Shida T, Kimura F, Shimizu H, Ohtsuka M, Nakatani Y, Miyazaki M (2009) Significance of monocyte chemoattractant protein-1 in angiogenesis and survival in colorectal liver metastases. Int J Oncol 34(4):923–930PubMedCrossRef
Yoshimoto K, Tajima H, Ohta T, Okamoto K, Sakai S, Kinoshita J, Furukawa H, Makino I, Hayashi H, Nakamura K, Oyama K, Inokuchi M, Nakagawara H, Itoh H, Fujita H, Takamura H, Ninomiya I, Kitagawa H, Fushida S, Fujimura T, Wakayama T, Iseki S, Shimizu K (2012) Increased E-selectin in hepatic ischemia-reperfusion injury mediates liver metastasis of pancreatic cancer. Oncol Rep 28(3):791–796PubMedPubMedCentral
Yu Y, Gao S, Li Q, Wang C, Lai X, Chen X, Wang R, Di J, Li T, Wang W, Wu X (2012) The FGF2-binding peptide P7 inhibits melanoma growth in vitro and in vivo. J Cancer Res Clin Oncol 138(8):1321–1328PubMedCrossRef
Zabel BA, Wang Y, Lewén S, Berahovich RD, Penfold ME, Zhang P, Powers J, Summers BC, Miao Z, Zhao B, Jalili A, Janowska-Wieczorek A, Jaen JC, Schall TJ (2009) Elucidation of CXCR7-mediated signaling events and inhibition of CXCR4-mediated tumor cell transendothelial migration by CXCR7 ligands. J Immunol 183(5):3204–3211PubMedCrossRef
Zelenay S, Lopes-Carvalho T, Caramalho I, Moraes-Fontes MF, Rebelo M, Demengeot J (2005) Foxp3+ CD25- CD4 T cells constitute a reservoir of committed regulatory cells that regain CD25 expression upon homeostatic expansion. Proc Natl Acad Sci U S A 102(11):4091–4096PubMedPubMedCentralCrossRef
Zeng J, Cai S, Yi Y, He Y, Wang Z, Jiang G, Li X, Du J (2009) Prevention of spontaneous tumor development in a ret transgenic mouse model by ret peptide vaccination with indoleamine 2,3-dioxygenase inhibitor 1-methyl tryptophan. Cancer Res 69(9):3963–3970PubMedCrossRef
Zervos EE, Shafii AE, Haq M, Rosemurgy AS (1999a) Matrix metalloproteinase inhibition suppresses MMP-2 activity and activation of PANC-1 cells in vitro. J Surg Res 84(2):162–167PubMedCrossRef
Zervos EE, Shafii AE, Rosemurgy AS (1999b) Matrix metalloproteinase (MMP) inhibition selectively decreases type II MMP activity in a murine model of pancreatic cancer. J Surg Res 81(1):65–68PubMedCrossRef
Zhou N, Luo Z, Luo J, Fan X, Cayabyab M, Hiraoka M, Liu D, Han X, Pesavento J, Dong CZ, Wang Y, An J, Kaji H, Sodroski JG, Huang Z (2002) Exploring the stereochemistry of CXCR4-peptide recognition and inhibiting HIV-1 entry with D-peptides derived from chemokines. J Biol Chem 277(20):17476–17485PubMedCrossRef
Zhu A, Zhan W, Liang Z, Yoon Y, Yang H, Grossniklaus HE, Xu J, Rojas M, Lockwood M, Snyder JP, Liotta DC, Shim H (2010) Dipyrimidine amines: a novel class of chemokine receptor type 4 antagonists with high specificity. J Med Chem 53(24):8556–8568PubMedPubMedCentralCrossRef
Zubeldia IG, Bleau AM, Redrado M, Serrano D, Agliano A, Gil-Puig C, Vidal-Vanaclocha F, Lecanda J, Calvo A (2013) Epithelial to mesenchymal transition and cancer stem cell phenotypes leading to liver metastasis are abrogated by the novel TGFβ1-targeting peptides P17 and P144. Exp Cell Res 319(3):12–22PubMedCrossRef
Metadata
Title
Process of hepatic metastasis from pancreatic cancer: biology with clinical significance
Authors
Haojun Shi
Ji Li
Deliang Fu
Publication date
01-06-2016
Publisher
Springer Berlin Heidelberg
Published in
Journal of Cancer Research and Clinical Oncology / Issue 6/2016
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-015-2024-0

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