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Cancer Microenvironment
Published in: Cancer Microenvironment 1/2010

01-12-2010 | Review Paper

The Tumor Microenvironment in Colorectal Carcinogenesis

Authors: Vijay G. Peddareddigari, Dingzhi Wang, Raymond N. DuBois

Published in: Cancer Microenvironment | Issue 1/2010

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Abstract

Colorectal cancer is the second leading cause of cancer-related mortality in the United States. Therapeutic developments in the past decade have extended life expectancy in patients with metastatic disease. However, metastatic colorectal cancers remain incurable. Numerous agents that were demonstrated to have significant antitumor activity in experimental models translated into disappointing results in extending patient survival. This has resulted in more attention being focused on the contribution of tumor microenvironment to the progression of a number of solid tumors including colorectal cancer. A more complete understanding of interactions between tumor epithelial cells and their stromal elements will enhance therapeutic options and improve clinical outcome. Here we will review the role of various stromal components in colorectal carcinogenesis and discuss the potential of targeting these components for the development of future therapeutic agents.
Literature
1.
Whitlock EP, Lin JS, Liles E et al (2008) Screening for colorectal cancer: a targeted, updated systematic review for the U.S. Preventive Services Task Force. Ann Intern Med 149(9):638–658PubMed
2.
Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70PubMed
3.
Mantovani A, Allavena P, Sica A et al (2008) Cancer-related inflammation. Nature 454(7203):436–444PubMed
4.
Colotta F, Allavena P, Sica A et al (2009) Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis 30(7):1073–1081PubMed
5.
DuBois RN, Giardiello FM, Smalley WE (1996) Nonsteroidal anti-inflammatory drugs, eicosanoids, and colorectal cancer prevention. Gastroenterol Clin North Am 25(4):773–791PubMed
6.
Wang D, DuBois RN (2008) Pro-inflammatory prostaglandins and progression of colorectal cancer. Cancer Lett 267(2):197–203PubMed
7.
Smalley WE, DuBois RN (1998) Colorectal cancer and nonsteroidal anti-inflammatory drugs. Adv Pharmacol 39:1–20
8.
Gupta RA, Dubois RN (2001) Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2. Nat Rev Cancer 1(1):11–21PubMed
9.
Eberhart CE, Coffey RJ, Radhika A et al (1994) Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 107(4):1183–1188PubMed
10.
Wang D, Dubois RN (2006) Prostaglandins and cancer. Gut 55(1):115–122PubMed
11.
Greenhough A, Smartt HJ, Moore AE et al (2009) The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment. Carcinogenesis 30(3):377–386PubMed
12.
DuBois RN, Radhika A, Reddy BS et al (1996) Increased cyclooxygenase-2 levels in carcinogen-induced rat colonic tumors. Gastroenterology 110(4):1259–1262PubMed
13.
Backlund MG, Mann JR, Dubois RN (2005) Mechanisms for the prevention of gastrointestinal cancer: the role of prostaglandin E2. Oncology 69(Suppl 1):28–32PubMed
14.
Rigas B, Goldman IS, Levine L (1993) Altered eicosanoid levels in human colon cancer. J Lab Clin Med 122(5):518–523PubMed
15.
Backlund MG, Mann JR, Holla VR et al (2005) 15-Hydroxyprostaglandin dehydrogenase is down-regulated in colorectal cancer. J Biol Chem 280(5):3217–3223PubMed
16.
Backlund MG, Mann JR, Wang D et al (2006) Ras up-regulation of cyclooxygenase-2. Methods Enzymol 407:401–410PubMed
17.
Williams CS, Mann M, DuBois RN (1999) The role of cyclooxygenases in inflammation, cancer, and development. Oncogene 18(55):7908–7916PubMed
18.
Tsujii M, Kawano S, Tsuji S et al (1998) Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 93(5):705–716PubMed
19.
Gout S, Huot J (2008) Role of cancer microenvironment in metastasis: focus on colon cancer. Cancer Microenviron 1(1):69–83PubMed
20.
Murdoch C, Muthana M, Coffelt SB et al (2008) The role of myeloid cells in the promotion of tumour angiogenesis. Nat Rev Cancer 8(8):618–631PubMed
21.
Green CE, Liu T, Montel V et al (2009) Chemoattractant signaling between tumor cells and macrophages regulates cancer cell migration, metastasis and neovascularization. PLoS One 4(8):e6713PubMed
22.
Tokunaga T, Oshika Y, Abe Y et al (1998) Vascular endothelial growth factor (VEGF) mRNA isoform expression pattern is correlated with liver metastasis and poor prognosis in colon cancer. Br J Cancer 77(6):998–1002PubMed
23.
Jedinak A, Dudhgaonkar S, Sliva D (2009) Activated macrophages induce metastatic behavior of colon cancer cells. Immunobiology. PMID: 19457576
24.
Zins K, Abraham D, Sioud M et al (2007) Colon cancer cell-derived tumor necrosis factor-alpha mediates the tumor growth-promoting response in macrophages by up-regulating the colony-stimulating factor-1 pathway. Cancer Res 67(3):1038–1045PubMed
25.
Wang D, Wang H, Brown J et al (2006) CXCL1 induced by prostaglandin E2 promotes angiogenesis in colorectal cancer. J Exp Med 203(4):941–951PubMed
26.
Okada F, Kawaguchi T, Habelhah H et al (2000) Conversion of human colonic adenoma cells to adenocarcinoma cells through inflammation in nude mice. Lab Invest 80(11):1617–1628PubMed
27.
de Visser KE, Eichten A, Coussens LM (2006) Paradoxical roles of the immune system during cancer development. Nat Rev Cancer 6(1):24–37PubMed
28.
Ishiguro K, Yoshida T, Yagishita H et al (2006) Epithelial and stromal genetic instability contributes to genesis of colorectal adenomas. Gut 55(5):695–702PubMed
29.
Lewis CE, Pollard JW (2006) Distinct role of macrophages in different tumor microenvironments. Cancer Res 66(2):605–612PubMed
30.
Sica A, Allavena P, Mantovani A (2008) Cancer related inflammation: the macrophage connection. Cancer Lett 267(2):204–215PubMed
31.
Sica A, Bronte V (2007) Altered macrophage differentiation and immune dysfunction in tumor development. J Clin Invest 117(5):1155–1166PubMed
32.
Fricke I, Gabrilovich DI (2006) Dendritic cells and tumor microenvironment: a dangerous liaison. Immunol Invest 35(3–4):459–483PubMed
33.
Sica A, Schioppa T, Mantovani A et al (2006) Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. Eur J Cancer 42(6):717–727PubMed
34.
Mantovani A, Sica A, Locati M (2007) New vistas on macrophage differentiation and activation. Eur J Immunol 37(1):14–16PubMed
35.
Mantovani A, Sica A, Sozzani S et al (2004) The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 25(12):677–686PubMed
36.
Van Ginderachter JA, Movahedi K, Van den Bossche J et al (2008) Macrophages, PPARs, and Cancer. PPAR Res 2008:169414PubMed
37.
Gordon S (2003) Alternative activation of macrophages. Nat Rev Immunol 3(1):23–35PubMed
38.
Xu W, Schlagwein N, Roos A et al (2007) Human peritoneal macrophages show functional characteristics of M-CSF-driven anti-inflammatory type 2 macrophages. Eur J Immunol 37(6):1594–1599PubMed
39.
Hamilton JA (2008) Colony-stimulating factors in inflammation and autoimmunity. Nat Rev Immunol 8(7):533–544PubMed
40.
Martinez FO, Gordon S, Locati M et al (2006) Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression. J Immunol 177(10):7303–7311PubMed
41.
Biswas SK, Gangi L, Paul S et al (2006) A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-kappaB and enhanced IRF-3/STAT1 activation). Blood 107(5):2112–2122PubMed
42.
Kristiansen M, Graversen JH, Jacobsen C et al (2001) Identification of the haemoglobin scavenger receptor. Nature 409(6817):198–201PubMed
43.
Stein M, Keshav S, Harris N et al (1992) Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation. J Exp Med 176(1):287–292PubMed
44.
Hagemann T, Wilson J, Burke F et al (2006) Ovarian cancer cells polarize macrophages toward a tumor-associated phenotype. J Immunol 176(8):5023–5032PubMed
45.
Xu W, Roos A, Schlagwein N et al (2006) IL-10-producing macrophages preferentially clear early apoptotic cells. Blood 107(12):4930–4937PubMed
46.
Savage ND, de Boer T, Walburg KV et al (2008) Human anti-inflammatory macrophages induce Foxp3+ GITR+ CD25+ regulatory T cells, which suppress via membrane-bound TGFbeta-1. J Immunol 181(3):2220–2226PubMed
47.
Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420(6917):860–867PubMed
48.
Paik S, Shak S, Tang G et al (2004) A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 351(27):2817–2826PubMed
49.
Bacman D, Merkel S, Croner R et al (2007) TGF-beta receptor 2 downregulation in tumour-associated stroma worsens prognosis and high-grade tumours show more tumour-associated macrophages and lower TGF-beta1 expression in colon carcinoma: a retrospective study. BMC Cancer 7:156PubMed
50.
Leek RD, Lewis CE, Whitehouse R (1996) Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Res 56(20):4625–4629PubMed
51.
Takanami I, Takeuchi K, Kodaira S (1999) Tumor-associated macrophage infiltration in pulmonary adenocarcinoma: association with angiogenesis and poor prognosis. Oncology 57(2):138–142PubMed
52.
Shieh YS, Hung YJ, Hsieh CB et al (2009) Tumor-associated macrophage correlated with angiogenesis and progression of mucoepidermoid carcinoma of salivary glands. Ann Surg Oncol 16(3):751–760PubMed
53.
Barbera-Guillem E, Nyhus JK, Wolford CC et al (2002) Vascular endothelial growth factor secretion by tumor-infiltrating macrophages essentially supports tumor angiogenesis, and IgG immune complexes potentiate the process. Cancer Res 62(23):7042–7049PubMed
54.
Condeelis J, Pollard JW (2006) Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell 124(2):263–266PubMed
55.
Lin EY, Li JF, Gnatovskiy L et al (2006) Macrophages regulate the angiogenic switch in a mouse model of breast cancer. Cancer Res 66(23):11238–11246PubMed
56.
Lin EY, Nguyen AV, Russell RG et al (2001) Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J Exp Med 193(6):727–740PubMed
57.
Zeisberger SM, Odermatt B, Marty C et al (2006) Clodronate-liposome-mediated depletion of tumour-associated macrophages: a new and highly effective antiangiogenic therapy approach. Br J Cancer 95(3):272–281PubMed
58.
Miselis NR, Wu ZJ, Van Rooijen N et al (2008) Targeting tumor-associated macrophages in an orthotopic murine model of diffuse malignant mesothelioma. Mol Cancer Ther 7(4):788–799PubMed
59.
Herbeuval JP, Lelievre E, Lambert C et al (2004) Recruitment of STAT3 for production of IL-10 by colon carcinoma cells induced by macrophage-derived IL-6. J Immunol 172(7):4630–4636PubMed
60.
Galizia G, Orditura M, Romano C et al (2002) Prognostic significance of circulating IL-10 and IL-6 serum levels in colon cancer patients undergoing surgery. Clin Immunol 102(2):169–178PubMed
61.
Popovic ZV, Sandhoff R, Sijmonsma TP et al (2007) Sulfated glycosphingolipid as mediator of phagocytosis: SM4s enhances apoptotic cell clearance and modulates macrophage activity. J Immunol 179(10):6770–6782PubMed
62.
Adegboyega PA, Ololade O, Saada J et al (2004) Subepithelial myofibroblasts express cyclooxygenase-2 in colorectal tubular adenomas. Clin Cancer Res 10(17):5870–5879PubMed
63.
Pollard JW (2004) Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer 4(1):71–78PubMed
64.
Sickert D, Aust DE, Langer S et al (2005) Characterization of macrophage subpopulations in colon cancer using tissue microarrays. Histopathology 46(5):515–521PubMed
65.
Burke B, Giannoudis A, Corke KP et al (2003) Hypoxia-induced gene expression in human macrophages: implications for ischemic tissues and hypoxia-regulated gene therapy. Am J Pathol 163(4):1233–1243PubMed
66.
Mizukami Y, Kohgo Y, Chung DC (2007) Hypoxia inducible factor-1 independent pathways in tumor angiogenesis. Clin Cancer Res 13(19):5670–5674PubMed
67.
Etoh T, Shibuta K, Barnard GF et al (2000) Angiogenin expression in human colorectal cancer: the role of focal macrophage infiltration. Clin Cancer Res 6(9):3545–3551PubMed
68.
Baier PK, Eggstein S, Wolff-Vorbeck G et al (2005) Chemokines in human colorectal carcinoma. Anticancer Res 25(5):3581–3584PubMed
69.
Kim SJ, Kim JS, Papadopoulos J et al (2009) Circulating monocytes expressing CD31: implications for acute and chronic angiogenesis. Am J Pathol 174(5):1972–1980PubMed
70.
Aharinejad S, Abraham D, Paulus P et al (2002) Colony-stimulating factor-1 antisense treatment suppresses growth of human tumor xenografts in mice. Cancer Res 62(18):5317–5324PubMed
71.
Bataille F, Rohrmeier C, Bates R et al (2008) Evidence for a role of epithelial mesenchymal transition during pathogenesis of fistulae in Crohn’s disease. Inflamm Bowel Dis 14(11):1514–1527PubMed
72.
Bates RC, Pursell BM, Mercurio AM (2007) Epithelial-mesenchymal transition and colorectal cancer: gaining insights into tumor progression using LIM 1863 cells. Cells Tissues Organs 185(1–3):29–39PubMed
73.
Bates RC, Mercurio AM (2003) Tumor necrosis factor-alpha stimulates the epithelial-to-mesenchymal transition of human colonic organoids. Mol Biol Cell 14(5):1790–1800PubMed
74.
Bates RC, DeLeo MJ III, Mercurio AM (2004) The epithelial-mesenchymal transition of colon carcinoma involves expression of IL-8 and CXCR-1-mediated chemotaxis. Exp Cell Res 299(2):315–324PubMed
75.
Liu G, Ding W, Liu X et al (2006) c-Fos is required for TGFbeta1 production and the associated paracrine migratory effects of human colon carcinoma cells. Mol Carcinog 45(8):582–593PubMed
76.
Paduch R, Kandefer-Szerszen M (2009) Transforming growth factor-beta1 (TGF-beta1) and acetylcholine (ACh) alter nitric oxide (NO) and interleukin-1beta (IL-1beta) secretion in human colon adenocarcinoma cells. In Vitro Cell Dev Biol Anim 45(9):543–550PubMed
77.
Mantovani A, Bottazzi B, Colotta F et al (1992) The origin and function of tumor-associated macrophages. Immunol Today 13(7):265–270PubMed
78.
Li F, Cao Y, Townsend CM Jr et al (2005) TGF-beta signaling in colon cancer cells. World J Surg 29(3):306–311PubMed
79.
Reinacher-Schick A, Baldus SE, Romdhana B et al (2004) Loss of Smad4 correlates with loss of the invasion suppressor E-cadherin in advanced colorectal carcinomas. J Pathol 202(4):412–420PubMed
80.
Thuault S, Tan EJ, Peinado H et al (2008) HMGA2 and Smads co-regulate SNAIL1 expression during induction of epithelial-to-mesenchymal transition. J Biol Chem 283(48):33437–33446PubMed
81.
Thuault S, Valcourt U, Petersen M et al (2006) Transforming growth factor-beta employs HMGA2 to elicit epithelial-mesenchymal transition. J Cell Biol 174(2):175–183PubMed
82.
Mook OR, Frederiks WM, Van Noorden CJ (2004) The role of gelatinases in colorectal cancer progression and metastasis. Biochim Biophys Acta 1705(2):69–89PubMed
83.
Illemann M, Bird N, Majeed A et al (2006) MMP-9 is differentially expressed in primary human colorectal adenocarcinomas and their metastases. Mol Cancer Res 4(5):293–302PubMed
84.
Gounaris E, Tung CH, Restaino C et al (2008) Live imaging of cysteine-cathepsin activity reveals dynamics of focal inflammation, angiogenesis, and polyp growth. PLoS One 3(8):e2916PubMed
85.
Mohamed MM, Sloane BF (2006) Cysteine cathepsins: multifunctional enzymes in cancer. Nat Rev Cancer 6(10):764–775PubMed
86.
Gocheva V, Joyce JA (2007) Cysteine cathepsins and the cutting edge of cancer invasion. Cell Cycle 6(1):60–64PubMed
87.
Harvey SR, Sait SN, Xu Y et al (1999) Demonstration of urokinase expression in cancer cells of colon adenocarcinomas by immunohistochemistry and in situ hybridization. Am J Pathol 155(4):1115–1120PubMed
88.
Laufs S, Schumacher J, Allgayer H (2006) Urokinase-receptor (u-PAR): an essential player in multiple games of cancer: a review on its role in tumor progression, invasion, metastasis, proliferation/dormancy, clinical outcome and minimal residual disease. Cell Cycle 5(16):1760–1771PubMed
89.
Lubbe WJ, Zuzga DS, Zhou Z et al (2009) Guanylyl cyclase C prevents colon cancer metastasis by regulating tumor epithelial cell matrix metalloproteinase-9. Cancer Res 69(8):3529–3536PubMed
90.
Sinnamon MJ, Carter KJ, Fingleton B et al (2008) Matrix metalloproteinase-9 contributes to intestinal tumourigenesis in the adenomatous polyposis coli multiple intestinal neoplasia mouse. Int J Exp Pathol 89(6):466–475PubMed
91.
Baier PK, Wolff-Vorbeck G, Eggstein S et al (2005) Cytokine expression in colon carcinoma. Anticancer Res 25(3B):2135–2139PubMed
92.
Mantovani A, Sozzani S, Locati M et al (2002) Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 23(11):549–555PubMed
93.
Sakaguchi S (2005) Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol 6(4):345–352PubMed
94.
Smyth MJ, Teng MW, Swann J et al (2006) CD4+CD25+ T regulatory cells suppress NK cell-mediated immunotherapy of cancer. J Immunol 176(3):1582–1587PubMed
95.
Sinicrope FA, Rego RL, Ansell SM, et al (2009) A low intraepithelial effector (CD3(+))/Regulatory (FoxP3(+)) T-cell ratio predicts adverse outcome of human colon carcinoma. Gastroenterology. 137(4):1270–1279
96.
Gabrilovich DI, Bronte V, Chen SH et al (2007) The terminology issue for myeloid-derived suppressor cells. Cancer Res 67(1):425, author reply 426PubMed
97.
Nagaraj S, Gabrilovich DI (2008) Tumor escape mechanism governed by myeloid-derived suppressor cells. Cancer Res 68(8):2561–2563PubMed
98.
Mandruzzato S, Solito S, Falisi E et al (2009) IL4Ralpha+ myeloid-derived suppressor cell expansion in cancer patients. J Immunol 182(10):6562–6568PubMed
99.
Ochoa AC, Zea AH, Hernandez C et al (2007) Arginase, prostaglandins, and myeloid-derived suppressor cells in renal cell carcinoma. Clin Cancer Res 13(2 Pt 2):721s–726sPubMed
100.
Almand B, Clark JI, Nikitina E et al (2001) Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J Immunol 166(1):678–689PubMed
101.
Diaz-Montero CM, Salem ML, Nishimura MI et al (2009) Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother 58(1):49–59PubMed
102.
Umemura N, Saio M, Suwa T et al (2008) Tumor-infiltrating myeloid-derived suppressor cells are pleiotropic-inflamed monocytes/macrophages that bear M1- and M2-type characteristics. J Leukoc Biol 83(5):1136–1144PubMed
103.
Gabrilovich DI, Nagaraj S (2009) Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9(3):162–174PubMed
104.
Cascio S, Ferla R, D’Andrea A et al (2009) Expression of angiogenic regulators, VEGF and leptin, is regulated by the EGF/PI3K/STAT3 pathway in colorectal cancer cells. J Cell Physiol 221(1):189–194PubMed
105.
Donkor MK, Lahue E, Hoke TA et al (2009) Mammary tumor heterogeneity in the expansion of myeloid-derived suppressor cells. Int Immunopharmacol 9(7–8):937–948PubMed
106.
Nagaraj S, Gupta K, Pisarev V et al (2007) Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer. Nat Med 13(7):828–835PubMed
107.
Huang B, Pan PY, Li Q et al (2006) Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host. Cancer Res 66(2):1123–1131PubMed
108.
Yang L, DeBusk LM, Fukuda K et al (2004) Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. Cancer Cell 6(4):409–421PubMed
109.
Movahedi K, Guilliams M, Van den Bossche J et al (2008) Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell-suppressive activity. Blood 111(8):4233–4244PubMed
110.
Sinha P, Clements VK, Fulton AM et al (2007) Prostaglandin E2 promotes tumor progression by inducing myeloid-derived suppressor cells. Cancer Res 67(9):4507–4513PubMed
111.
Zhang Y, Liu Q, Zhang M et al (2009) Fas signal promotes lung cancer growth by recruiting myeloid-derived suppressor cells via cancer cell-derived PGE2. J Immunol 182(6):3801–3808PubMed
112.
Kormelink TG, Abudukelimu A, Redegeld FA (2009) Mast cells as target in cancer therapy. Curr Pharm Des 15(16):1868–1878
113.
Ribatti D, Vacca A, Nico B et al (2001) The role of mast cells in tumour angiogenesis. Br J Haematol 115(3):514–521PubMed
114.
Crivellato E, Nico B, Ribatti D (2008) Mast cells and tumour angiogenesis: new insight from experimental carcinogenesis. Cancer Lett 269(1):1–6PubMed
115.
Fisher ER, Paik SM, Rockette H et al (1989) Prognostic significance of eosinophils and mast cells in rectal cancer: findings from the National Surgical Adjuvant Breast and Bowel Project (protocol R-01). Hum Pathol 20(2):159–163PubMed
116.
Gulubova M, Vlaykova T (2009) Prognostic significance of mast cell number and microvascular density for the survival of patients with primary colorectal cancer. J Gastroenterol Hepatol 24(7):1265–1275PubMed
117.
Huang B, Lei Z, Zhang GM et al (2008) SCF-mediated mast cell infiltration and activation exacerbate the inflammation and immunosuppression in tumor microenvironment. Blood 112(4):1269–1279PubMed
118.
Grutzkau A, Kruger-Krasagakes S, Baumeister H et al (1998) Synthesis, storage, and release of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) by human mast cells: implications for the biological significance of VEGF206. Mol Biol Cell 9(4):875–884PubMed
119.
Qu Z, Liebler JM, Powers MR et al (1995) Mast cells are a major source of basic fibroblast growth factor in chronic inflammation and cutaneous hemangioma. Am J Pathol 147(3):564–573PubMed
120.
Lin XP, Liu WX, Li J (2004) The study on expression of bFGF and quantity of mast cell in infant hemangiomas of grandulae parotid gland. Shanghai Kou Qiang Yi Xue 13(3):167, 172, 178PubMed
121.
Hallgren J, Estrada S, Karlson U et al (2001) Heparin antagonists are potent inhibitors of mast cell tryptase. Biochemistry 40(24):7342–7349PubMed
122.
Pejler G, Sadler JE (1999) Mechanism by which heparin proteoglycan modulates mast cell chymase activity. Biochemistry 38(37):12187–12195PubMed
123.
Bowrey PF, King J, Magarey C et al (2000) Histamine, mast cells and tumour cell proliferation in breast cancer: does preoperative cimetidine administration have an effect? Br J Cancer 82(1):167–170PubMed
124.
Dvorak AM (2005) Mast cell-derived mediators of enhanced microvascular permeability, vascular permeability factor/vascular endothelial growth factor, histamine, and serotonin, cause leakage of macromolecules through a new endothelial cell permeability organelle, the vesiculo-vacuolar organelle. Chem Immunol Allergy 85:185–204PubMed
125.
Nakae S, Suto H, Berry GJ et al (2007) Mast cell-derived TNF can promote Th17 cell-dependent neutrophil recruitment in ovalbumin-challenged OTII mice. Blood 109(9):3640–3648PubMed
126.
Kneilling M, Mailhammer R, Hultner L et al (2009) Direct crosstalk between mast cell-TNF and TNFR1-expressing endothelia mediates local tissue inflammation. Blood 114(8):1696–1706PubMed
127.
Nakayama T, Yao L, Tosato G (2004) Mast cell-derived angiopoietin-1 plays a critical role in the growth of plasma cell tumors. J Clin Invest 114(9):1317–1325PubMed
128.
Ribatti D, Crivellato E (2009) The controversial role of mast cells in tumor growth. Int Rev Cell Mol Biol 275:89–131PubMed
129.
Ribatti D, Crivellato E, Molica S (2009) Mast cells and angiogenesis in haematological malignancies. Leuk Res 33(7):876–879PubMed
130.
Coussens LM, Raymond WW, Bergers G et al (1999) Inflammatory mast cells up-regulate angiogenesis during squamous epithelial carcinogenesis. Genes Dev 13(11):1382–1397PubMed
131.
Gounaris E, Erdman SE, Restaino C et al (2007) Mast cells are an essential hematopoietic component for polyp development. Proc Natl Acad Sci U S A 104(50):19977–19982PubMed
132.
Kashiwase Y, Inamura H, Morioka J et al (2008) Quantitative analysis of mast cells in benign and malignant colonic lesions: immunohistochemical study on formalin-fixed, paraffin-embedded tissues. Allergol Immunopathol (Madr) 36(5):271–276
133.
Taweevisit M (2006) The association of stromal mast cell response and tumor cell differentiation in colorectal cancer. J Med Assoc Thai 89(Suppl 3):S69–S73PubMed
134.
Yoshii M, Jikuhara A, Mori S et al (2005) Mast cell tryptase stimulates DLD-1 carcinoma through prostaglandin- and MAP kinase-dependent manners. J Pharmacol Sci 98(4):450–458PubMed
135.
Maltby S, Khazaie K, McNagny KM (2009) Mast cells in tumor growth: angiogenesis, tissue remodelling and immune-modulation. Biochim Biophys Acta 1796(1):19–26PubMed
136.
Nakae S, Suto H, Iikura M et al (2006) Mast cells enhance T cell activation: importance of mast cell costimulatory molecules and secreted TNF. J Immunol 176(4):2238–2248PubMed
137.
Simson L, Ellyard JI, Dent LA et al (2007) Regulation of carcinogenesis by IL-5 and CCL11: a potential role for eosinophils in tumor immune surveillance. J Immunol 178(7):4222–4229PubMed
138.
Hart PH, Townley SL, Grimbaldeston MA et al (2002) Mast cells, neuropeptides, histamine, and prostaglandins in UV-induced systemic immunosuppression. Methods 28(1):79–89PubMed
139.
Harizi H, Juzan M, Pitard V et al (2002) Cyclooxygenase-2-issued prostaglandin e(2) enhances the production of endogenous IL-10, which down-regulates dendritic cell functions. J Immunol 168(5):2255–2263PubMed
140.
Sinnamon MJ, Carter KJ, Sims LP et al (2008) A protective role of mast cells in intestinal tumorigenesis. Carcinogenesis 29(4):880–886PubMed
141.
Noviana D, Kono F, Nagakui Y et al (2001) Distribution and enzyme histochemical characterisation of mast cells in cats. Histochem J 33(11–12):597–603PubMed
142.
Shimizu H, Nagakui Y, Tsuchiya K et al (2001) Demonstration of chymotryptic and tryptic activities in mast cells of rodents: comparison of 17 species of the family Muridae. J Comp Pathol 125(1):76–79PubMed
143.
Kitamura T, Kometani K, Hashida H et al (2007) SMAD4-deficient intestinal tumors recruit CCR1+ myeloid cells that promote invasion. Nat Genet 39(4):467–475PubMed
144.
Drew E, Huettner CS, Tenen DG et al (2005) CD34 expression by mast cells: of mice and men. Blood 106(5):1885–1887PubMed
145.
Drew E, Merkens H, Chelliah S et al (2002) CD34 is a specific marker of mature murine mast cells. Exp Hematol 30(10):1211PubMed
146.
Drew E, Merzaban JS, Seo W et al (2005) CD34 and CD43 inhibit mast cell adhesion and are required for optimal mast cell reconstitution. Immunity 22(1):43–57PubMed
147.
Tanaka A, Yamane Y, Matsuda H (2001) Mast cell MMP-9 production enhanced by bacterial lipopolysaccharide. J Vet Med Sci 63(7):811–813PubMed
148.
Linnekin D (1999) Early signaling pathways activated by c-Kit in hematopoietic cells. Int J Biochem Cell Biol 31(10):1053–1074PubMed
149.
Berger SA, Mak TW, Paige CJ (1994) Leukocyte common antigen (CD45) is required for immunoglobulin E-mediated degranulation of mast cells. J Exp Med 180(2):471–476PubMed
150.
Kalluri R, Zeisberg M (2006) Fibroblasts in cancer. Nat Rev Cancer 6(5):392–401PubMed
151.
Ostman A, Augsten M (2009) Cancer-associated fibroblasts and tumor growth—bystanders turning into key players. Curr Opin Genet Dev 19(1):67–73PubMed
152.
Sugimoto H, Mundel TM, Kieran MW et al (2006) Identification of fibroblast heterogeneity in the tumor microenvironment. Cancer Biol Ther 5(12):1640–1646PubMed
153.
Henry LR, Lee HO, Lee JS et al (2007) Clinical implications of fibroblast activation protein in patients with colon cancer. Clin Cancer Res 13(6):1736–1741PubMed
154.
Nakagawa H, Liyanarachchi S, Davuluri RV et al (2004) Role of cancer-associated stromal fibroblasts in metastatic colon cancer to the liver and their expression profiles. Oncogene 23(44):7366–7377PubMed
155.
Mueller L, Goumas FA, Affeldt M et al (2007) Stromal fibroblasts in colorectal liver metastases originate from resident fibroblasts and generate an inflammatory microenvironment. Am J Pathol 171(5):1608–1618PubMed
156.
Direkze NC, Hodivala-Dilke K, Jeffery R et al (2004) Bone marrow contribution to tumor-associated myofibroblasts and fibroblasts. Cancer Res 64(23):8492–8495PubMed
157.
Yang L, Lin C, Liu ZR (2006) P68 RNA helicase mediates PDGF-induced epithelial mesenchymal transition by displacing Axin from beta-catenin. Cell 127(1):139–155PubMed
158.
Joesting MS, Perrin S, Elenbaas B et al (2005) Identification of SFRP1 as a candidate mediator of stromal-to-epithelial signaling in prostate cancer. Cancer Res 65(22):10423–10430PubMed
159.
Zhu CQ, Popova SN, Brown ER et al (2007) Integrin alpha 11 regulates IGF2 expression in fibroblasts to enhance tumorigenicity of human non-small-cell lung cancer cells. Proc Natl Acad Sci U S A 104(28):11754–11759PubMed
160.
Taniwaki K, Fukamachi H, Komori K et al (2007) Stroma-derived matrix metalloproteinase (MMP)-2 promotes membrane type 1-MMP-dependent tumor growth in mice. Cancer Res 67(9):4311–4319PubMed
161.
Orimo A, Gupta PB, Sgroi DC et al (2005) Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 121(3):335–348PubMed
162.
Orimo A, Weinberg RA (2006) Stromal fibroblasts in cancer: a novel tumor-promoting cell type. Cell Cycle 5(15):1597–1601PubMed
163.
Konstantinopoulos PA, Vandoros GP, Karamouzis MV et al (2007) EGF-R is expressed and AP-1 and NF-kappaB are activated in stromal myofibroblasts surrounding colon adenocarcinomas paralleling expression of COX-2 and VEGF. Cell Oncol 29(6):477–482PubMed
164.
Vandoros GP, Konstantinopoulos PA, Sotiropoulou-Bonikou G et al (2006) PPAR-gamma is expressed and NF-kB pathway is activated and correlates positively with COX-2 expression in stromal myofibroblasts surrounding colon adenocarcinomas. J Cancer Res Clin Oncol 132(2):76–84PubMed
165.
Fodde R, Smits R, Clevers H (2001) APC, signal transduction and genetic instability in colorectal cancer. Nat Rev Cancer 1(1):55–67PubMed
166.
Fodde R, Brabletz T (2007) Wnt/beta-catenin signaling in cancer stemness and malignant behavior. Curr Opin Cell Biol 19(2):150–158PubMed
167.
Le NH, Franken P, Fodde R (2008) Tumour-stroma interactions in colorectal cancer: converging on beta-catenin activation and cancer stemness. Br J Cancer 98(12):1886–1893PubMed
168.
Eisinger AL, Nadauld LD, Shelton DN et al (2006) The adenomatous polyposis coli tumor suppressor gene regulates expression of cyclooxygenase-2 by a mechanism that involves retinoic acid. J Biol Chem 281(29):20474–20482PubMed
169.
Eisinger AL, Prescott SM, Jones DA et al (2007) The role of cyclooxygenase-2 and prostaglandins in colon cancer. Prostaglandins Other Lipid Mediat 82(1–4):147–154PubMed
170.
Wang D, Mann JR, DuBois RN (2004) WNT and cyclooxygenase-2 cross-talk accelerates adenoma growth. Cell Cycle 3(12):1512–1515PubMed
171.
Wang D, Wang H, Shi Q et al (2004) Prostaglandin E(2) promotes colorectal adenoma growth via transactivation of the nuclear peroxisome proliferator-activated receptor delta. Cancer Cell 6(3):285–295PubMed
172.
Kitadai Y, Sasaki T, Kuwai T et al (2006) Expression of activated platelet-derived growth factor receptor in stromal cells of human colon carcinomas is associated with metastatic potential. Int J Cancer 119(11):2567–2574PubMed
173.
Kitadai Y, Sasaki T, Kuwai T et al (2006) Targeting the expression of platelet-derived growth factor receptor by reactive stroma inhibits growth and metastasis of human colon carcinoma. Am J Pathol 169(6):2054–2065PubMed
174.
Crawford Y, Kasman I, Yu L et al (2009) PDGF-C mediates the angiogenic and tumorigenic properties of fibroblasts associated with tumors refractory to anti-VEGF treatment. Cancer Cell 15(1):21–34PubMed
175.
Francia G, Emmenegger U, Kerbel RS (2009) Tumor-associated fibroblasts as “Trojan Horse” mediators of resistance to anti-VEGF therapy. Cancer Cell 15(1):3–5PubMed
176.
De Palma M, Venneri MA, Galli R et al (2005) Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors. Cancer Cell 8(3):211–226PubMed
177.
Venneri MA, De Palma M, Ponzoni M et al (2007) Identification of proangiogenic TIE2-expressing monocytes (TEMs) in human peripheral blood and cancer. Blood 109(12):5276–5285PubMed
178.
Murdoch C, Tazzyman S, Webster S et al (2007) Expression of Tie-2 by human monocytes and their responses to angiopoietin-2. J Immunol 178(11):7405–7411PubMed
179.
Lewis CE, De Palma M, Naldini L (2007) Tie2-expressing monocytes and tumor angiogenesis: regulation by hypoxia and angiopoietin-2. Cancer Res 67(18):8429–8432PubMed
180.
Ellis LM, Ahmad S, Fan F et al (2002) Angiopoietins and their role in colon cancer angiogenesis. Oncology (Williston Park) 16(4 Suppl 3):31–35
181.
De Palma M, Naldini L (2009) Tie2-expressing monocytes (TEMs): novel targets and vehicles of anticancer therapy? Biochim Biophys Acta 1796(1):5–10PubMed
182.
Sarraf-Yazdi S, Mi J, Moeller BJ et al (2008) Inhibition of in vivo tumor angiogenesis and growth via systemic delivery of an angiopoietin 2-specific RNA aptamer. J Surg Res 146(1):16–23PubMed
183.
Eck M, Schmausser B, Scheller K et al (2003) Pleiotropic effects of CXC chemokines in gastric carcinoma: differences in CXCL8 and CXCL1 expression between diffuse and intestinal types of gastric carcinoma. Clin Exp Immunol 134(3):508–515PubMed
184.
Roncucci L, Mora E, Mariani F et al (2008) Myeloperoxidase-positive cell infiltration in colorectal carcinogenesis as indicator of colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 17(9):2291–2297PubMed
185.
Roessner A, Kuester D, Malfertheiner P et al (2008) Oxidative stress in ulcerative colitis-associated carcinogenesis. Pathol Res Pract 204(7):511–524PubMed
186.
Xie K (2001) Interleukin-8 and human cancer biology. Cytokine Growth Factor Rev 12(4):375–391PubMed
187.
Tazzyman S, Lewis CE, Murdoch C (2009) Neutrophils: key mediators of tumour angiogenesis. Int J Exp Pathol 90(3):222–231PubMed
188.
Queen MM, Ryan RE, Holzer RG et al (2005) Breast cancer cells stimulate neutrophils to produce oncostatin M: potential implications for tumor progression. Cancer Res 65(19):8896–8904PubMed
189.
Hawinkels LJ, Zuidwijk K, Verspaget HW et al (2008) VEGF release by MMP-9 mediated heparan sulphate cleavage induces colorectal cancer angiogenesis. Eur J Cancer 44(13):1904–1913PubMed
190.
McCourt M, Wang JH, Sookhai S et al (1999) Proinflammatory mediators stimulate neutrophil-directed angiogenesis. Arch Surg 134(12):1325–1331, discussion 1331–1322PubMed
191.
Cassatella MA (1999) Neutrophil-derived proteins: selling cytokines by the pound. Adv Immunol 73:369–509PubMed
192.
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):12493–12498PubMed
193.
Knaapen AM, Schins RP, Polat D et al (2002) Mechanisms of neutrophil-induced DNA damage in respiratory tract epithelial cells. Mol Cell Biochem 234–235(1–2):143–151PubMed
194.
Vermeer IT, Henderson LY, Moonen EJ et al (2004) Neutrophil-mediated formation of carcinogenic N-nitroso compounds in an in vitro model for intestinal inflammation. Toxicol Lett 154(3):175–182PubMed
195.
Ten Kate M, Aalbers AG, Sluiter W et al (2007) Polymorphonuclear leukocytes increase the adhesion of circulating tumor cells to microvascular endothelium. Anticancer Res 27(1A):17–22PubMed
196.
van den Tol MP, ten Raa S, van Grevenstein WM et al (2007) The post-surgical inflammatory response provokes enhanced tumour recurrence: a crucial role for neutrophils. Dig Surg 24(5):388–394PubMed
197.
Di Carlo E, Forni G, Lollini P et al (2001) The intriguing role of polymorphonuclear neutrophils in antitumor reactions. Blood 97(2):339–345PubMed
198.
di Carlo E, Iezzi M, Pannellini T et al (2001) Neutrophils in anti-cancer immunological strategies: old players in new games. J Hematother Stem Cell Res 10(6):739–748PubMed
199.
Scapini P, Lapinet-Vera JA, Gasperini S et al (2000) The neutrophil as a cellular source of chemokines. Immunol Rev 177:195–203PubMed
200.
van Gisbergen KP, Geijtenbeek TB, van Kooyk Y (2005) Close encounters of neutrophils and DCs. Trends Immunol 26(12):626–631PubMed
201.
Fridlender ZG, Sun J, Kim S et al (2009) Polarization of tumor-associated neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN. Cancer Cell 16(3):183–194PubMed
202.
Pages F, Berger A, Camus M et al (2005) Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med 353(25):2654–2666PubMed
203.
Morris M, Platell C, Iacopetta B (2008) Tumor-infiltrating lymphocytes and perforation in colon cancer predict positive response to 5-fluorouracil chemotherapy. Clin Cancer Res 14(5):1413–1417PubMed
204.
Galon J, Costes A, Sanchez-Cabo F et al (2006) Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313(5795):1960–1964PubMed
205.
Waldner M, Schimanski CC, Neurath MF (2006) Colon cancer and the immune system: the role of tumor invading T cells. World J Gastroenterol 12(45):7233–7238PubMed
206.
Gounaris E, Blatner NR, Dennis K et al (2009) T-regulatory cells shift from a protective anti-inflammatory to a cancer-promoting proinflammatory phenotype in polyposis. Cancer Res 69(13):5490–5497PubMed
207.
Colombo MP, Piconese S (2009) Polyps wrap mast cells and Treg within tumorigenic tentacles. Cancer Res 69(14):5619–5622PubMed
208.
Yaqub S, Henjum K, Mahic M et al (2008) Regulatory T cells in colorectal cancer patients suppress anti-tumor immune activity in a COX-2 dependent manner. Cancer Immunol Immunother 57(6):813–821PubMed
209.
Lonnroth C, Andersson M, Arvidsson A et al (2008) Preoperative treatment with a non-steroidal anti-inflammatory drug (NSAID) increases tumor tissue infiltration of seemingly activated immune cells in colorectal cancer. Cancer Immun 8:5PubMed
210.
Roux S, Apetoh L, Chalmin F et al (2008) CD4+CD25+ Tregs control the TRAIL-dependent cytotoxicity of tumor-infiltrating DCs in rodent models of colon cancer. J Clin Invest 118(11):3751–3761PubMed
211.
Shah S, Divekar AA, Hilchey SP et al (2005) Increased rejection of primary tumors in mice lacking B cells: inhibition of anti-tumor CTL and TH1 cytokine responses by B cells. Int J Cancer 117(4):574–586PubMed
212.
Lanier LL (2003) Natural killer cell receptor signaling. Curr Opin Immunol 15(3):308–314PubMed
213.
Moriwaki K, Noda K, Furukawa Y et al (2009) Deficiency of GMDS leads to escape from NK cell-mediated tumor surveillance through modulation of TRAIL signaling. Gastroenterology 137(1):188–198, 198 e181–182PubMed
214.
Whiteside TL, Vujanovic NL, Herberman RB (1998) Natural killer cells and tumor therapy. Curr Top Microbiol Immunol 230:221–244PubMed
215.
Doubrovina ES, Doubrovin MM, Vider E et al (2003) Evasion from NK cell immunity by MHC class I chain-related molecules expressing colon adenocarcinoma. J Immunol 171(12):6891–6899PubMed
216.
Ryan AE, Shanahan F, O’Connell J et al (2006) Fas ligand promotes tumor immune evasion of colon cancer in vivo. Cell Cycle 5(3):246–249PubMed
217.
O’Callaghan G, Kelly J, Shanahan F et al (2008) Prostaglandin E2 stimulates Fas ligand expression via the EP1 receptor in colon cancer cells. Br J Cancer 99(3):502–512PubMed
218.
Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392(6673):245–252PubMed
219.
Pockaj BA, Basu GD, Pathangey LB et al (2004) Reduced T-cell and dendritic cell function is related to cyclooxygenase-2 overexpression and prostaglandin E2 secretion in patients with breast cancer. Ann Surg Oncol 11(3):328–339PubMed
220.
Gabrilovich D, Ishida T, Oyama T et al (1998) Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood 92(11):4150–4166PubMed
221.
Curiel TJ, Cheng P, Mottram P et al (2004) Dendritic cell subsets differentially regulate angiogenesis in human ovarian cancer. Cancer Res 64(16):5535–5538PubMed
222.
Wu YG, Wu GZ, Wang L, et al (2009) Tumor cell lysate-pulsed dendritic cells induce a T cell response against colon cancer in vitro and in vivo. Med Oncol. PMID: 19669608
223.
Verheul HM, Pinedo HM (1998) Tumor growth: a putative role for platelets? Oncologist 3(2):IIPubMed
224.
Nash GF, Turner LF, Scully MF et al (2002) Platelets and cancer. Lancet Oncol 3(7):425–430PubMed
225.
Karpatkin S (2003) Role of thrombin in tumor angiogenesis, implantation, and metastasis. Pathophysiol Haemost Thromb 33(Suppl 1):54–55PubMed
226.
Falanga A, Rickles FR (1999) Pathophysiology of the thrombophilic state in the cancer patient. Semin Thromb Hemost 25(2):173–182PubMed
227.
Nash GF, Walsh DC, Kakkar AK (2001) The role of the coagulation system in tumour angiogenesis. Lancet Oncol 2(10):608–613PubMed
228.
Stellos K, Bigalke B, Langer H et al (2009) Expression of stromal-cell-derived factor-1 on circulating platelets is increased in patients with acute coronary syndrome and correlates with the number of CD34+ progenitor cells. Eur Heart J 30(5):584–593PubMed
229.
Kopp HG, Placke T, Salih HR (2009) Platelet-derived transforming growth factor-{beta} down-regulates NKG2D thereby inhibiting natural killer cell antitumor reactivity. Cancer Res 69(19):7775–7783PubMed
230.
McCarty OJ, Mousa SA, Bray PF et al (2000) Immobilized platelets support human colon carcinoma cell tethering, rolling, and firm adhesion under dynamic flow conditions. Blood 96(5):1789–1797PubMed
231.
Burdick MM, Konstantopoulos K (2004) Platelet-induced enhancement of LS174T colon carcinoma and THP-1 monocytoid cell adhesion to vascular endothelium under flow. Am J Physiol Cell Physiol 287(2):C539–C547PubMed
232.
Ricci-Vitiani L, Fabrizi E, Palio E et al (2009) Colon cancer stem cells. J Mol Med 87(11):1097–1104PubMed
233.
Lin EH, Hassan M, Li Y et al (2007) Elevated circulating endothelial progenitor marker CD133 messenger RNA levels predict colon cancer recurrence. Cancer 110(3):534–542PubMed
234.
Kemp KC, Hows J, Donaldson C (2005) Bone marrow-derived mesenchymal stem cells. Leuk Lymphoma 46(11):1531–1544PubMed
235.
Pittenger MF, Mackay AM, Beck SC et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284(5411):143–147PubMed
236.
Prockop DJ (1997) Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276(5309):71–74PubMed
237.
Hall B, Andreeff M, Marini F (2007) The participation of mesenchymal stem cells in tumor stroma formation and their application as targeted-gene delivery vehicles. Handb Exp Pharmacol 180:263–283PubMed
238.
Karnoub AE, Dash AB, Vo AP et al (2007) Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 449(7162):557–563PubMed
239.
Nauta AJ, Kruisselbrink AB, Lurvink E et al (2006) Mesenchymal stem cells inhibit generation and function of both CD34+-derived and monocyte-derived dendritic cells. J Immunol 177(4):2080–2087PubMed
240.
Nauta AJ, Fibbe WE (2007) Immunomodulatory properties of mesenchymal stromal cells. Blood 110(10):3499–3506PubMed
241.
Sanz L, Santos-Valle P, Alonso-Camino V et al (2008) Long-term in vivo imaging of human angiogenesis: critical role of bone marrow-derived mesenchymal stem cells for the generation of durable blood vessels. Microvasc Res 75(3):308–314PubMed
242.
Ning H, Yang F, Jiang M et al (2008) The correlation between cotransplantation of mesenchymal stem cells and higher recurrence rate in hematologic malignancy patients: outcome of a pilot clinical study. Leukemia 22(3):593–599PubMed
243.
Kerbel RS (2008) Tumor angiogenesis. N Engl J Med 358(19):2039–2049PubMed
244.
Choi HJ, Hyun MS, Jung GJ et al (1998) Tumor angiogenesis as a prognostic predictor in colorectal carcinoma with special reference to mode of metastasis and recurrence. Oncology 55(6):575–581PubMed
245.
Liao D, Johnson RS (2007) Hypoxia: a key regulator of angiogenesis in cancer. Cancer Metastasis Rev 26(2):281–290PubMed
246.
Fukuda R, Kelly B, Semenza GL (2003) Vascular endothelial growth factor gene expression in colon cancer cells exposed to prostaglandin E2 is mediated by hypoxia-inducible factor 1. Cancer Res 63(9):2330–2334PubMed
247.
Finetti F, Donnini S, Giachetti A et al (2009) Prostaglandin E2 primes the angiogenic switch via a synergic interaction with the endothelial fibroblast growth factor-2 pathway. Circ Res 105(7):657–666PubMed
248.
Gao J, Knutsen A, Arbman G et al (2009) Clinical and biological significance of angiogenesis and lymphangiogenesis in colorectal cancer. Dig Liver Dis 41(2):116–122PubMed
249.
Onogawa S, Kitadai Y, Tanaka S et al (2004) Regulation of vascular endothelial growth factor (VEGF)-C and VEGF-D expression by the organ microenvironment in human colon carcinoma. Eur J Cancer 40(10):1604–1609PubMed
250.
Tammela T, Petrova TV, Alitalo K (2005) Molecular lymphangiogenesis: new players. Trends Cell Biol 15(8):434–441PubMed
251.
Tammela T, Saaristo A, Lohela M et al (2005) Angiopoietin-1 promotes lymphatic sprouting and hyperplasia. Blood 105(12):4642–4648PubMed
252.
Kazama S, Watanabe T, Kanazawa T et al (2007) Vascular endothelial growth factor-C (VEGF-C) is a more specific risk factor for lymph node metastasis than VEGF-D in submucosal colorectal cancer. Hepatogastroenterology 54(73):71–76PubMed
253.
Timpl R, Dziadek M (1986) Structure, development, and molecular pathology of basement membranes. Int Rev Exp Pathol 29:1–112PubMed
254.
Hagios C, Lochter A, Bissell MJ (1998) Tissue architecture: the ultimate regulator of epithelial function? Philos Trans R Soc Lond B Biol Sci 353(1370):857–870PubMed
255.
Rabinovitz I, Mercurio AM (1997) The integrin alpha6beta4 functions in carcinoma cell migration on laminin-1 by mediating the formation and stabilization of actin-containing motility structures. J Cell Biol 139(7):1873–1884PubMed
256.
Zapatka M, Zboralski D, Radacz Y et al (2007) Basement membrane component laminin-5 is a target of the tumor suppressor Smad4. Oncogene 26(10):1417–1427PubMed
257.
Tsuruta D, Kobayashi H, Imanishi H et al (2008) Laminin-332-integrin interaction: a target for cancer therapy? Curr Med Chem 15(20):1968–1975PubMed
258.
Kirkland SC (2009) Type I collagen inhibits differentiation and promotes a stem cell-like phenotype in human colorectal carcinoma cells. Br J Cancer 101(2):320–326PubMed
259.
Ding J, Li D, Wang X et al (2008) Fibronectin promotes invasiveness and focal adhesion kinase tyrosine phosphorylation of human colon cancer cell. Hepatogastroenterology 55(88):2072–2076PubMed
260.
Hashimoto Y, Skacel M, Adams JC (2008) Association of loss of epithelial syndecan-1 with stage and local metastasis of colorectal adenocarcinomas: an immunohistochemical study of clinically annotated tumors. BMC Cancer 8:185PubMed
261.
Theocharis AD (2002) Human colon adenocarcinoma is associated with specific post-translational modifications of versican and decorin. Biochim Biophys Acta 1588(2):165–172PubMed
262.
Toole BP (2004) Hyaluronan: from extracellular glue to pericellular cue. Nat Rev Cancer 4(7):528–539PubMed
263.
Toole BP, Wight TN, Tammi MI (2002) Hyaluronan-cell interactions in cancer and vascular disease. J Biol Chem 277(7):4593–4596PubMed
264.
Kim HR, Wheeler MA, Wilson CM et al (2004) Hyaluronan facilitates invasion of colon carcinoma cells in vitro via interaction with CD44. Cancer Res 64(13):4569–4576PubMed
265.
Laurich C, Wheeler MA, Iida J et al (2004) Hyaluronan mediates adhesion of metastatic colon carcinoma cells. J Surg Res 122(1):70–74PubMed
266.
Dunn KM, Lee PK, Wilson CM et al (2009) Inhibition of hyaluronan synthases decreases matrix metalloproteinase-7 (MMP-7) expression and activity. Surgery 145(3):322–329PubMed
267.
Misra S, Toole BP, Ghatak S (2006) Hyaluronan constitutively regulates activation of multiple receptor tyrosine kinases in epithelial and carcinoma cells. J Biol Chem 281(46):34936–34941PubMed
268.
Ghatak S, Misra S, Toole BP (2005) Hyaluronan constitutively regulates ErbB2 phosphorylation and signaling complex formation in carcinoma cells. J Biol Chem 280(10):8875–8883PubMed
269.
Misra S, Obeid LM, Hannun YA et al (2008) Hyaluronan constitutively regulates activation of COX-2-mediated cell survival activity in intestinal epithelial and colon carcinoma cells. J Biol Chem 283(21):14335–14344PubMed
270.
Yazawa K, Tsuno NH, Kitayama J et al (2005) Selective inhibition of cyclooxygenase-2 inhibits colon cancer cell adhesion to extracellular matrix by decreased expression of beta1 integrin. Cancer Sci 96(2):93–99PubMed
271.
Heino J, Kapyla J (2009) Cellular receptors of extracellular matrix molecules. Curr Pharm Des 15(12):1309–1317PubMed
272.
Broom OJ, Massoumi R, Sjolander A (2006) Alpha2beta1 integrin signalling enhances cyclooxygenase-2 expression in intestinal epithelial cells. J Cell Physiol 209(3):950–958PubMed
273.
Murillo CA, Rychahou PG, Evers BM (2004) Inhibition of alpha5 integrin decreases PI3K activation and cell adhesion of human colon cancers. Surgery 136(2):143–149PubMed
274.
van Kempen LC, de Visser KE, Coussens LM (2006) Inflammation, proteases and cancer. Eur J Cancer 42(6):728–734PubMed
275.
Zucker S, Vacirca J (2004) Role of matrix metalloproteinases (MMPs) in colorectal cancer. Cancer Metastasis Rev 23(1–2):101–117PubMed
276.
Toda D, Ota T, Tsukuda K et al (2006) Gefitinib decreases the synthesis of matrix metalloproteinase and the adhesion to extracellular matrix proteins of colon cancer cells. Anticancer Res 26(1A):129–134PubMed
277.
Davidsen ML, Wurtz SO, Romer MU et al (2006) TIMP-1 gene deficiency increases tumour cell sensitivity to chemotherapy-induced apoptosis. Br J Cancer 95(8):1114–1120PubMed
278.
Sorensen NM, Bystrom P, Christensen IJ et al (2007) TIMP-1 is significantly associated with objective response and survival in metastatic colorectal cancer patients receiving combination of irinotecan, 5-fluorouracil, and folinic acid. Clin Cancer Res 13(14):4117–4122PubMed
279.
Packer LM, Williams SJ, Callaghan S et al (2004) Expression of the cell surface mucin gene family in adenocarcinomas. Int J Oncol 25(4):1119–1126PubMed
280.
Baldus SE, Monig SP, Huxel S et al (2004) MUC1 and nuclear beta-catenin are coexpressed at the invasion front of colorectal carcinomas and are both correlated with tumor prognosis. Clin Cancer Res 10(8):2790–2796PubMed
281.
Huang J, Che MI, Huang YT et al (2009) Overexpression of MUC15 activates extracellular signal-regulated kinase 1/2 and promotes the oncogenic potential of human colon cancer cells. Carcinogenesis 30(8):1452–1458PubMed
282.
Wai PY, Kuo PC (2004) The role of osteopontin in tumor metastasis. J Surg Res 121(2):228–241PubMed
283.
El-Tanani MK (2008) Role of osteopontin in cellular signaling and metastatic phenotype. Front Biosci 13:4276–4284PubMed
284.
Wai PY, Mi Z, Guo H et al (2005) Osteopontin silencing by small interfering RNA suppresses in vitro and in vivo CT26 murine colon adenocarcinoma metastasis. Carcinogenesis 26(4):741–751PubMed
285.
Irby RB, McCarthy SM, Yeatman TJ (2004) Osteopontin regulates multiple functions contributing to human colon cancer development and progression. Clin Exp Metastasis 21(6):515–523PubMed
286.
Zagani R, Hamzaoui N, Cacheux W et al (2009) Cyclooxygenase-2 inhibitors down-regulate osteopontin and Nr4a2—new therapeutic targets for colorectal cancers. Gastroenterology 137(4):1358–1366PubMed
287.
Iacovazzi PA, Notarnicola M, Caruso MG, et al (2009) Serum levels of galectin-3 and its ligand 90 k/mac-2 bp in colorectal cancer patients. Immunopharmacol Immunotoxicol. PMID: 19686089
288.
Song S, Mazurek N, Liu C et al (2009) Galectin-3 mediates nuclear beta-catenin accumulation and Wnt signaling in human colon cancer cells by regulation of glycogen synthase kinase-3beta activity. Cancer Res 69(4):1343–1349PubMed
289.
Nobumoto A, Nagahara K, Oomizu S et al (2008) Galectin-9 suppresses tumor metastasis by blocking adhesion to endothelium and extracellular matrices. Glycobiology 18(9):735–744PubMed
290.
Kikuchi Y, Kashima TG, Nishiyama T et al (2008) Periostin is expressed in pericryptal fibroblasts and cancer-associated fibroblasts in the colon. J Histochem Cytochem 56(8):753–764PubMed
291.
Ma C, Rong Y, Radiloff DR et al (2008) Extracellular matrix protein betaig-h3/TGFBI promotes metastasis of colon cancer by enhancing cell extravasation. Genes Dev 22(3):308–321PubMed
Metadata
Title
The Tumor Microenvironment in Colorectal Carcinogenesis
Authors
Vijay G. Peddareddigari
Dingzhi Wang
Raymond N. DuBois
Publication date
01-12-2010
Publisher
Springer Netherlands
Published in
Cancer Microenvironment / Issue 1/2010
Print ISSN: 1875-2292
Electronic ISSN: 1875-2284
DOI
https://doi.org/10.1007/s12307-010-0038-3

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Chemokines and Cancer Progression: A Qualitative Review on the Role of Stromal Cell-derived Factor 1-alpha and CXCR4 in Endometrial Cancer

Conference Report

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Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
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