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Cellular Oncology
Published in: Cellular Oncology 5/2016

Open Access 01-10-2016 | Review

The role of lymphangiogenesis and angiogenesis in tumor metastasis

Author: Roman Paduch

Published in: Cellular Oncology | Issue 5/2016

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Abstract

Background

Metastasis is the main cause of mortality in cancer patients. Two major routes of cancer cell spread are currently being recognized: dissemination via blood vessels (hematogenous spread) and dissemination via the lymphatic system (lymphogenous spread). Here, our current knowledge on the role of both blood and lymphatic vessels in cancer cell metastasis is summarized. In addition, I will discuss why cancer cells select one or both of the two routes to disseminate and I will provide a short description of the passive and active models of intravasation. Finally, lymphatic vessel density (LVD), blood vessel density (BVD), interstitial fluid pressure (IFP) and tumor hypoxia, as well as regional lymph node metastasis and the recently discovered primo vascular system (PVS) will be highlighted as important factors influencing tumor cell motility and spread and, ultimately, clinical outcome.

Conclusions

Lymphangiogenesis and angiogenesis are important phenomena involved in the spread of cancer cells and they are associated with a poor prognosis. It is anticipated that new discoveries and advancing knowledge on these phenomena will allow an improvement in the treatment of cancer patients.
Literature
1.
Z. Cao, B. Shang, G. Zhang, L. Miele, F.H. Sarkar, Z. Wang, Q. Zhou, Tumor cell-mediated neovascularization and lymphangiogenesis contrive tumor progression and cancer metastasis. Biochim. Biophys. Acta 1836, 273–286 (2013)PubMed
2.
Y. You, H. Li, X. Qin, Y. Zhang, W. Song, Y. Ran, F. Gao, Decreased CDK10 expression correlates with lymph node metastasis and predicts poor outcome in breast cancer patients—a short report. Cell. Oncol. 38, 485–491 (2015)CrossRef
3.
S. Wan, Y. Liu, Y. Weng, W. Wang, W. Ren, C. Fei, Y. Chen, Z. Zhang, T. Wang, J. Wang, Y. Jiang, L. Zhou, T. He, Y. Zhang, BMP9 regulates cross-talk between breast cancer cells and bone marrow-derived mesenchymal stem cells. Cell. Oncol. 37, 363–375 (2014)CrossRef
4.
S.A. Stacker, M.E. Baldwin, M.G. Achen, The role of tumor lymphangiogenesis in metastasic spread. FASEB J. 16, 922–934 (2002)PubMedCrossRef
5.
A. Khosravi, S. Shahrabi, M. Shahjahani, N. Saki, The bone marrow metastasis niche in retinoblastoma. Cell. Oncol. 38, 253–263 (2015)CrossRef
6.
M.S. Pepper, Lymphangiogenesis and tumor metastasis: myth or reality? Clin. Cancer Res. 7, 462–468 (2001)PubMed
7.
M.S. Pepper, J.-C. Tille, R. Nisato, M. Skobe, Lymphangiogenesis and tumor metastasis. Cell Tissue Res. 314, 167–177 (2003)PubMedCrossRef
8.
M. Andrade, A. Jacomo, Anatomy of the Human Lymphatic System, in Cancer Metastasis and the Lymphovascular System. Basis for Rational Therapy, ed. by S.P.L. Leong (Springer Science + Business Media, LCC, New York, 2007), pp. 55–77CrossRef
9.
W. Thiele, J.P. Sleeman, Tumor-induced lymphangiogenesis: a target for cancer therapy? J. Biotechnol. 124, 224–241 (2006)PubMedCrossRef
10.
J.S. Reis-Filho, F.C. Schmitt, Lymphangiogenesis in tumors: what do we know? Microsc. Res. Tech. 60, 171–180 (2003)PubMedCrossRef
11.
N.E. Tobler, M. Detmar, Tumor and lymph node lymphangiogensesis – impact on cancer metastasis. J. Leukoc. Biol. 80, 691–696 (2006)PubMedCrossRef
12.
I. Van der Auwera, Y. Cao, J.C. Tille, M.S. Pepper, D.G. Jackson, S.B. Fox, A.L. Harris, L.Y. Dirix, P.B. Vermeulen, First international consensus on the methodology of lymphangiogenesis quantification in solid human tumors. Br. J. Cancer 95, 1611–1625 (2006)PubMedPubMedCentralCrossRef
13.
M.A. Swartz, M. Skobe, Lymphatic function, lymphangiogenesis, and cancer metastasis. Microsc. Res. Tech. 55, 92–99 (2001)PubMedCrossRef
14.
S.B. Seidelmann, J.K. Lighthouse, D.M. Greif, Development and pathologies of the arterial wall. Cell. Mol. Life Sci. 71, 1977–1999 (2014)PubMedCrossRef
15.
S. Szala, M. Jarosz, Nowotworowe naczynia krwionośne. Postepy Hig. Med. Dosw. 65, 437–446 (2011)CrossRef
16.
X.-F. Sun, H. Zhang, Clinicopathological significance of stromal variables: angiogenesis, lymphangiogenesis, inflammatory infiltration, MMP and PINCH in colorectal carcinomas. Mol. Cancer 5, 20 pages (2006)
17.
S. Ran, L. Volk, K. Hall, M.J. Flister, Lymphangiogenesis and lymphatic metastasis in breast cancer. Pathophysiology 17, 229–251 (2010)PubMedCrossRef
18.
19.
A. Ålgars, M. Karikoski, G.G. Yegutkin, P. Stoitzner, J. Niemelä, M. Salmi, S. Jalkanen, Different role of CD73 in leukocyte trafficking via blood and lymph vessels. Blood 117, 4387–4393 (2011)PubMedCrossRef
20.
M. Wu, H.B. Frieboes, S.R. McDougall, M.A.J. Chaplain, V. Cristini, J. Lowengrub, The effect of interstitial pressure on tumor growth: coupling with the blood and lymphatic vascular systems. J. Theor. Biol. 320, 131–151 (2013)PubMedCrossRef
21.
G. Azzali, On the transendothelial passage of tumor cell from extravasal matrix into the lumen of absorbing lymphatic vessel. Microvasc. Res. 72, 74–85 (2006)PubMedCrossRef
22.
M.G. Achen, B.K. McColl, S.A. Stacker, Focus on lymphangiogenesis in tumor metastasis. Cancer Cell 7, 121–127 (2005)PubMedCrossRef
23.
M. Bockhorn, R.K. Jain, L.L. Munn, Active or passive mechanisms in metastasis: do cancer cells crawl into vessels, or are they pushed? Lancet Oncol. 8, 444–448 (2007)PubMedPubMedCentralCrossRef
24.
M.D. Hale, J.D. Hayden, H.I. Grabsch, Tumour-microenvironment interactions: role of tumour stroma and proteins produced by cancer-associated fibroblasts in chemotherapy response. Cell. Oncol. 36, 95–112 (2013)CrossRef
25.
D. Yao, C. Dai, S. Peng, Mechanism of the mesenchymal–epithelial transition and its relationship with metastatic tumor formation. Mol. Cancer Res. 9, 1608–1620 (2011)PubMedCrossRef
26.
27.
28.
M. Zeisberg, J.S. Duffield, Resolved: EMT produces fibroblasts in the kidney. J. Am. Soc. Nephrol. 21, 1247–1253 (2010)PubMedCrossRef
29.
J.J. Christiansen, A.K. Rajasekaran, Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis. Cancer Res. 66, 8319–8326 (2006)PubMedCrossRef
30.
31.
A. Stockinger, A. Eger, J. Wolf, H. Beug, R. Foisner, E-cadherin regulates cell growth by modulating proliferationdependent beta-catenin transcriptional activity. J. Cell Biol. 154, 1185–1196 (2001)PubMedPubMedCentralCrossRef
32.
33.
H.G. Kang, J.M. Jenabi, J. Zhang, N. Keshelava, H. Shimada, W.A. May, T. Ng, C.P. Reynolds, T.J. Triche, P.H.B. Sorensen, E-cadherin cell-cell adhesion in ewing tumor cells mediates suppression of anoikis through activation of the ErbB4 tyrosine kinase. Cancer Res. 67, 3094–3105 (2007)PubMedPubMedCentralCrossRef
34.
P. Reddy, L. Liu, C. Ren, P. Lindgren, K. Boman, Y. Shen, E. Lundin, U. Ottander, M. Rytinki, K. Liu, Formation of E-cadherin-mediated cell-cell adhesion activates AKT and mitogen activated protein kinase via phosphatidylinositol 3 kinase and ligand-independent activation of epidermal growth factor receptor in ovarian cancer cells. Mol. Endocrinol. 19, 2564–2578 (2005)PubMedCrossRef
35.
A. Wells, C. Yates, C.R. Shepard, E-cadherin as an indicator of mesenchymal to epithelial reverting transitions during the metastasis seeding of disseminated carcinomas. Clin. Exp. Metastasis 25, 621–628 (2008)PubMedPubMedCentralCrossRef
36.
L. Ding, Z. Zhang, D. Shang, J. Cheng, H. Yuan, Y. Wu, X. Song, H. Jiang, α-Smooth muscle actin-positive myofibroblasts, In association with epithelial–mesenchymal transition and lymphogenesis, is a critical prognostic parameter in patients with oral tongue squamous cell carcinoma. J. Oral Pathol. Med. 43, 335–343 (2014)PubMedCrossRef
37.
D.G. Jackson, R. Prevo, S. Clasper, S. Banerji, LYVE-1, the lymphatic system and tumor lymphangiogenesis. Trends Immunol. 22, 317–321 (2001)PubMedCrossRef
38.
39.
C. Zhou, J. Liu, Y. Tang, X. Liang, Inflammation linking EMT and cancer stem cells. Oral Oncol. 48, 1068–1075 (2012)PubMedCrossRef
40.
F.A. Malik, A.J. Sanders, W.G. Jiang, KAI-1/CD82, The molecule and clinical implication in cancer and cancer metastasis. Histol. Histopathol. 24, 519–530 (2009)PubMed
41.
L. Zhou, L. Yu, S. Wu, Z. Feng, W. Song, X. Gong, Clinicopathological significance of KAI1expression and epithelial-mesenchymal transition in non-small cell lung cancer. World J. Surg. Oncol. 13, 234–241 (2015)PubMedPubMedCentralCrossRef
42.
43.
J. Banyard, I. Chung, M. Migliozzi, D.T. Phan, A.M. Wilson, B.R. Zetter, D.R. Bielenberg, Identification of genes regulating migration and invasion using a new model of metastatic prostate cancer. BMC Cancer 14, Article No. 387 (2014)
44.
J. Banyard, I. Chung, A.M. Wilson, G. Vetter, A. Le Bechec, D.R. Bielenberg, B.R. Zetter, Regulation of epithelial plasticity by miR-424 and miR-200 in a new prostate cancer metastasis model. Sci. Rep. 3, Article No. 3151 (2013)
45.
O.H. Ocana, R. Corcoles, A. Fabra, G. Moreno-Bueno, H. Acloque, S. Vega, A. Barrallo-Gimeno, A. Cano, M.A. Nieto, Metastasis colonization requires the repression of the epithelial-mesenchymal transition inducer Prrx1. Cancer Cell 22, 709–724 (2012)PubMedCrossRef
46.
47.
H. Luo, G. Tu, Z. Liu, M. Liu, Cancer-associated fibroblasts: a multifaceted driver of breastcancer progression. Cancer Lett. 361, 155–163 (2015)PubMedCrossRef
48.
49.
50.
Y.Z. Lima, A.P. Southa, Tumour-stroma crosstalk in the development of squamous cell carcinoma. Int. J. Biochem. Cell Biol. 53, 450–458 (2014)CrossRef
51.
52.
N. Ilan, M. Elkin, I. Vlodavsky, Regulation, function and clinical significance of heparanase in cancer metastasis and angiogenesis. Int. J. Biochem. Cell Biol. 38, 2018–2039 (2006)PubMedCrossRef
53.
54.
55.
A. Orimo, P.B. Gupta, D.C. Sgroi, F. Arenzana-Seisdedos, T. Delaunay, R. Naeem, V.J. Carey, A.L. Richardson, R.A. Weinberg, Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 121, 335–348 (2005)PubMedCrossRef
56.
M. Quante, S.P. Tu, H. Tomita, T. Gonda, S.S.W. Wang, S. Takashi, G.H. Baik, W. Shibata, B. Diprete, K.S. Betz, R. Friedman, A. Varro, B. Tycko, T.C. Wang, Bone marrow-derived myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth. Cancer Cell 19, 257–272 (2011)PubMedPubMedCentralCrossRef
57.
N.G. Singer, A.I. Caplan, Mesenchymal stem cells: mechanisms of inflammation. Annu. Rev. Pathol. 6, 457–478 (2011)PubMedCrossRef
58.
P. Kamarajan, Y. Kapila, An altered fibronectin matrix induces anoikis of humansquamous cell carcinoma cells by suppressing integrin alpha v levels and phosphorylation of FAK and ERK. Apoptosis 12, 2221–2231 (2007)PubMedCrossRef
59.
C. Kainz, P. Kohlberger, C. Tempfer, G. Sliutz, G. Gitsch, A. Reinthaller, G. Breitenecker, Prognostic value of CD44 splice variants in human stage III cervical cancer. Eur. J. Cancer 31A, 1706–1709 (1995)PubMedCrossRef
60.
N.J. Nasser, Heparanase involvement in physiology and disease. Cell. Mol. Life Sci. 65, 1706–1715 (2008)PubMedCrossRef
61.
R. Stauder, W. Eisterer, J. Thaler, U. Günthert, CD44 variant isoforms in non-Hodgkin’s lymphoma: a new independent prognostic factor. Blood 85, 2885–2899 (1995)PubMed
62.
63.
G.E. Davis, D.R. Senger, Endothelial extracellular matrix: biosynthesis, remodeling, and functions during vascular morphogenesis and neovessel stabilization. Circ. Res. 97, 1093–1107 (2005)PubMedCrossRef
64.
65.
66.
X.Z. Huang, J.F. Wu, R. Ferrando, J.H. Lee, Y.L. Wang, R.V. Farese Jr., D. Sheppard, Fatal bilateral chylothorax in mice lacking the integrin α9β1. Mol. Cell. Biol. 20, 5208–5215 (2000)PubMedPubMedCentralCrossRef
67.
M. Wu, Y. Du, Y. Liu, Y. He, C. Yang, W. Wang, F. Gao, Low molecular weight hyaluronan induces lymphangiogenesis through LYVE-1-mediated signaling pathways. PLoS ONE 9, e92857 (2014)PubMedPubMedCentralCrossRef
68.
C. Danussi, P. Spessotto, A. Petrucco, B. Wassermann, P. Sabatelli, M. Montesi, R. Doliana, G.M. Bressan, A. Colombatti, Emilin1 deficiency causes structural and functional defects of lymphatic vasculature. Mol. Cell. Biol. 28, 4026–4039 (2008)PubMedPubMedCentralCrossRef
69.
S. Ingvarsen, A. Porse, C. Erpicum, L. Maertens, H.J. Jürgensen, D.H. Madsen, M.C. Melander, H. Gårdsvoll, G. Høyer-Hansen, A. Noel, K. Holmbeck, L.H. Engelholm, N. Behrendt, Targeting a single function of the multifunctional matrix metalloprotease MT1-MMP. Impact on lymphangiogenesis. J. Biol. Chem. 288, 10195–10204 (2013)PubMedPubMedCentralCrossRef
70.
Q. Wu, X. Li, H. Yang, C. Lu, J. You, Z. Zhang, Extracellular matrix protein 1 is correlated to carcinogenesis and lymphatic metastasis of human gastric cancer. World J. Surg. Oncol. 12, 132–139 (2014)PubMedPubMedCentralCrossRef
71.
B.C. Dobner, A.I. Riechardt, A.M. Joussen, S. Englert, N.E. Bechrakis, Expression of haematogenous and lymphogenous chemokine receptors and their ligands on uveal melanoma in association with liver metastasis. Acta Ophthalmol. 90, e638–e644 (2012)PubMedCrossRef
72.
73.
M. Langheinrich, V. Schellerer, K. Oeckl, M. Stürzl, E. Naschberger, R. Croner, Molecular mechanisms of lymphatic metastasis. Colorectal Cancer Book 1, 285–298 (2011)
74.
M.C. Langheinrich, V. Schellerer, A. Perrakis, C. Lohmüller, C. Schildberg, E. Naschberger, M. Stürzl, W. Hohenberger, R.S. Croner, Molecular mechanisms of lymphatic metastasis in solid tumors of the gastrointestinal tract. Int. J. Clin. Exp. Pathol. 5, 614–623 (2012)PubMedPubMedCentral
75.
Y. Morita, K. Hata, M. Nakanishi, T. Omata, N. Morita, Y. Yura, R. Nishimura, T. Yoneda, Cellular fibronectin 1 promotes VEGF-C expression, lymphangiogenesis and lymph node metastasis associated with human oral squamous cell carcinoma. Clin. Exp. Metastasis 32, 739–753 (2015)PubMedCrossRef
76.
L.-C. Du, X.-C. Chen, D. Wang, Y.-J. Wen, C.-T. Wang, X.-M. Wang, B. Kan, Y.-Q. Wei, X. Zhao, VEGF-D-induced draining lymphatic enlargement and tumor lymphangiogenesis promote lymph node metastasis in a xenograft model of ovarian carcinoma. Reprod. Biol. Endocrinol. 12, 14–24 (2014)PubMedPubMedCentralCrossRef
77.
I. Gisterek, R. Matkowski, J. Koźlak, D. Duś, A. Lacko, J. Szelachowska, J. Kornafel, Evaluation of prognostic value of VEGF-C and VEGF-D in breast cancer - 10 years follow-up analysis. Anticancer Res. 27, 2797–2802 (2007)PubMed
78.
R.A. Mohammed, A. Green, S. El-Shikh, E.C. Paish, I.O. Ellis, S.G. Martin, Prognostic significance of vascular endothelial cell growth factors -A, -C and -D in breast cancer and their relationship with angio- and lymphangiogenesis. Br. J. Cancer 96, 1092–1100 (2007)PubMedPubMedCentralCrossRef
79.
Y.C. Zhao, X.J. Ni, M.H. Wang, X.M. Zha, Y. Zhao, S. Wang, Tumor-derived VEGF-C, but not VEGF-D, promotes sentinel lymph node lymphangiogenesis prior to metastasis in breast cancer patients. Med. Oncol. 29, 2594–2600 (2012)PubMedCrossRef
80.
Y. He, T. Karpanen, K. Alitalo, Role of lymphangiogenic factors in tumor metastasis. Biochim. Biophys. Acta 1654, 3–12 (2004)PubMed
81.
Y. He, K. Kozaki, T. Karpanen, K. Koshikawa, S. Yla-Herttuala, T. Takahashi, K. Alitalo, Suppression of tumor lymphangiogenesis and lymph node metastasis by blocking vascular endothelial growth factor receptor 3 signaling. J. Natl. Cancer Inst. 94, 819–825 (2002)PubMedCrossRef
82.
G.G. Van den Eynden, I. Van der Auwera, S.J. Van Laere, X.B. Trinh, C.G. Colpaert, P. van Dam, L.Y. Dirix, P.B. Vermeulen, E.A. Van Marck, Comparison of molecular determinants of angiogenesis and lymphangiogenesis in lymph node metastases and in primary tumours of patients with breast cancer. J. Pathol. 213, 56–64 (2007)PubMedCrossRef
83.
M. Esposito, Y. Kang, Targeting tumor–stromal interactions in bone metastasis. Pharmacol. Ther. 141, 222–233 (2014)PubMedCrossRef
84.
F.G. Gomes, F. Nedel, A.M. Alves, J.E. Nör, S.B.C. Tarquinio, Tumor angiogenesis and lymphangiogenesis: tumor/endothelial crosstalk and cellular/environmental signaling mechanisms. Life Sci. 92, 101–107 (2013)PubMedCrossRef
85.
N. Wakisaka, Y. Hasegawa, S. Yoshimoto, K. Miura, A. Shiotani, J. Yokoyama, M. Sugasawa, M. Moriyama-Kita, K. Endo, T. Yoshizaki, Primary tumor-secreted lymphangiogenic factors induce pre-metastatic lymphvascular niche formation at sentinel lymph nodes in oral squamous cell carcinoma. PLoS ONE 10, e0144056 (2015)PubMedPubMedCentralCrossRef
86.
S.L. Schlereth, S. Iden, M. Mescher, B.R. Ksander, J.J. Bosch, C. Cursiefen, L.M. Heindl, A novel model of metastatic conjunctival melanoma in immune-competent mice. Invest. Ophthalmol. Vis. Sci. 56, 5965–5973 (2015)PubMedCrossRef
87.
T. Duong, P. Koopman, M. Francois, Tumor lymphangiogenesis as a potential therapeutic target. J. Oncol. Article ID 204946, 23 pages (2012)
88.
S. Hirakawa, From tumor lymphangiogenesis to lymphvascular niche. Cancer Sci. 100, 983–989 (2009)PubMedCrossRef
89.
K. Vazquez-Santillan, J. Melendez-Zajgla, L. Jimenez-Hernandez, G. Martínez-Ruiz, V. Maldonado, NF-κB signaling in cancer stem cells: a promising therapeutic target? Cell. Oncol. 38, 327–339 (2015)CrossRef
90.
J. Wilting, M. Papoutsi, K. Buttler, J. Becker, Embrionic Development of the Lymphovascular System and Tumor Lymphangiogenesis, in Cancer Metastasis and the Lymphovascular System. Basis for Rational Therapy, ed. by S.P.L. Leong (Springer Science + Business Media, LCC, New York, 2007), pp. 17–24CrossRef
91.
T. Li, J. Yang, Q. Zhou, Y. He, Molecular regulation of lymphangiogenesis in development and tumor microenvironment. Cancer Microenviron 5, 249–260 (2012)PubMedPubMedCentralCrossRef
92.
Z. Lokmic, E.S. Ng, M. Burton, E.G. Stanley, A.J. Penington, A.G. Elefanty, Isolation of human lymphatic endothelial cells by multi-parameter fluorescence-activated cell sorting. J. Vis. Exp. 99, e52691 (2015)PubMed
93.
G.L. Semenza, Cancer–stromal cell interactions mediated by hypoxia-inducible factors promote angiogenesis, lymphangiogenesis, and metastasis. Oncogene 32, 4057–4063 (2013)PubMedCrossRef
94.
J. Zhan, Y. Li, J. Yu, Y. Zhao, W. Cao, J. Ma, X. Sun, L. Sun, H. Qian, W. Zhu, W. Xu, Culture medium of bone marrow-derived human mesenchymal stem cells effects lymphatic endothelial cells and tumor lymph vessel formation. Oncol. Lett. 9, 1221–1226 (2015)PubMedPubMedCentral
95.
H. Ding, J. Cai, M. Mao, Y. Fang, Z. Huang, J. Jia, T. Li, L. Xu, J. Wang, J. Zhou, Q. Yang, Z. Wang, Tumor-associated macrophages induce lymphangiogenesis in cervical cancer via interaction with tumor cells. APMIS 122, 1059–1069 (2014)PubMedCrossRef
96.
R.-C. Ji, Macrophages are important mediators of either tumor- or inflammation-induced lymphangiogenesis. Cell. Mol. Life Sci. 69, 897–914 (2012)PubMedCrossRef
97.
M.-X. Da, Z. Wu, H.-W. Tian, Tumor lymphangiogenesis and lymphangiogenesis growth factors. Arch. Med. Res. 39, 365–372 (2008)PubMedCrossRef
98.
M.S. Kluger, O.R. Colegio, Lymphangiogenesis linked to VEGF-C from tumor-associated macrophages: Accomplices to metastasis by cutaneous squamous cell carcinoma. J. Invest. Dermatol. 131, 17–19 (2011)PubMedCrossRef
99.
C. Scavelli, A. Vacca, G. Di Pietro, F. Dammacco, D. Ribatti, Crosstalk between angiogenesis and lymphangiogenesis in tumor progression. Leukemia 18, 1054–1058 (2004)PubMedCrossRef
100.
E. Sundlisæter, A. Dicko, P.Ø. Sakariassen, K. Sondenaa, P.Ø. Enger, R. Bjerkvig, Lymphangiogenesis in colorectal cancer – prognostic and therapeutic aspects. Int. J. Cancer 121, 1401–1409 (2007)PubMedCrossRef
101.
S. Amatschek, E. Kriehuber, W. Bauer, B. Reininger, P. Meraner, A. Wolpl, N. Schwifer, C. Haslinger, G. Stingl, D. Maurer, Blood and lymphatic endothelial cell-specyfic differentiation programs are stringently controlled by the tissue environment. Blood 109, 4777–4785 (2007)PubMedCrossRef
102.
L. Esak, N.B. Pandey, A.S. Popel, Cross talk between cancer cells and blood endothelial and lymphatic endothelial cells in tumour and organ microenvironment. Expert Rev. Mol. Med. 17, 18 pages (2015)
103.
S.D. Nathanson, Preclinical Models of Regional Lymph Node Tumor Metastasis, in Cancer Metastasis and the Lymphovascular System. Basis for Rational Therapy, ed. by S.P.L. Leong (Springer Science + Business Media, LCC, New York, 2007), pp. 129–156CrossRef
104.
C.P. Ng, C.-L.E. Helm, M.A. Swartz, Interstitial flow differentially stimulates blood and lymphatic endothelial cell morphogenesis in vitro. Microvasc. Res. 68, 258–264 (2004)PubMedCrossRef
105.
S. Eccles, L. Paon, J. Sleeman, Lymphatic metastasis in breast cancer: importance and new insights into cellular and molecular mechanisms. Clin. Exp. Metastasis 24, 619–636 (2007)PubMedCrossRef
106.
R. Clarijs, D.J. Ruiter, R.M.W. de Waal, Lymphangiogenesis in malignant tumours: does it occur? J. Pathol. 193, 143–146 (2001)PubMedCrossRef
107.
D. Massi, Ö. Gököz, The biological significance of lymphangiogenesis in human tumors. Diagn. Histopathol. 16, 295–305 (2010)CrossRef
108.
109.
R.-C. Ji, Lymphatic endothelial cells, tumor lymphangiogenesis and metastasis: new insights into intratumoral and peritumoral lymphatics. Cancer Metastasis Rev. 25, 677–694 (2006)PubMedCrossRef
110.
D.G. Jackson, Lymphatic Markers, Tumour Lymphangiogenesis and Lymph Node Metastasis, in Cancer Metastasis and the Lymphovascular System. Basis for Rational Therapy, ed. by S.P.L. Leong (Springer Science + Business Media, LCC, New York, 2007), pp. 39–53CrossRef
111.
J.D. White, P.W. Hewett, D. Kosuge, T. McCulloch, B.C. Enholm, J. Carmichael, J.C. Murray, Vascular endothelial growth factor-D expression is an independent prognostic marker for survival in colorectal carcinoma. Cancer Res. 62, 1669–1675 (2002)PubMed
112.
S. El-Gendi, M. Abdel-Hadi, Lymphatic vessel density as prognostic factor in breast carcinoma: relation to clinicopathologic parameters. J. Egypt. Natl. Canc. Inst. 21, 139–149 (2009)PubMed
113.
K. Matsumoto, Y. Nakayama, Y. Inoue, N. Minagawa, T. Katsuki, K. Shibao, Y. Tsurudome, K. Hirata, N. Nagata, H. Itoh, Lymphatic microvessel density is an independent prognostic factor in colorectal cancer. Dis. Colon Rectum 50, 308–314 (2007)PubMedCrossRef
114.
J. Wang, Y. Guo, B. Wang, J. Bi, K. Li, X. Liang, H. Chu, H. Jiang, Lymphatic microvessel density and vascular endothelial growth factor-C and -D as prognostic factors in breast cancer: a systematic review and meta-analysis of the literature. Mol. Biol. Rep. 39, 11153–11165 (2012)PubMedCrossRef
115.
J. Wang, K. Li, B. Wang, J. Bi, Lymphatic microvessel density as a prognostic factor in non-small cell lung carcinoma: a meta-analysis of the literature. Mol. Biol. Rep. 39, 5331–5338 (2012)PubMedCrossRef
116.
I. Pastushenko, P.B. Vermeulen, F.J. Carapeto, G. Van den Eynden, A. Rutten, M. Ara, L.Y. Dirix, S. Van Laere, Blood microvessel density, lymphatic microvessel density and lymphatic invasion in predicting melanoma metastases: systematic review and meta-analysis. Br. J. Dermatol. 170, 66–77 (2014)PubMedCrossRef
117.
S. Yang, H. Cheng, J. Cai, L. Cai, J. Zhang, Z. Wang, PlGF expression in pre-invasive and invasive lesions of uterine cervix is associated with angiogenesis and lymphangiogenesis. APMIS 117, 831–838 (2009)PubMedCrossRef
118.
M. Nagahashi, S. Ramachandran, O.M. Rashid, K. Takabe, Lymphangiogenesis: a new player in cancer progression. World J. Gastroenterol. 28, 4003–4012 (2010)CrossRef
119.
M. Mohammadi, P. Chena, Effect of microvascular distribution and its density on interstitial fluid pressure in solid tumors: a computational model. Microvasc. Res. 101, 26–32 (2015)PubMedCrossRef
120.
A.S. Narang, S. Varia, Role of tumor vascular architecture in drug delivery. Adv. Drug Deliv. Rev. 63, 640–658 (2011)PubMedCrossRef
121.
S.J. Lunt, T.M.K. Kalliomaki, A. Brown, V.X. Yang, M. Milosevic, R.P. Hill, Interstitial fluid pressure, vascularity and metastasis in ectopic, orthotopic and spontaneous tumours. BMC Cancer 8, 2–15 (2008)PubMedPubMedCentralCrossRef
122.
X. Zhao, B. Sun, Y. Liu, D. Zhang, Z. Liu, X. Zhao, Q. Gu, H. Ch, X. Dong, N. Che, J. An, Y. Zheng, T. Liu, Linearly patterned programmed cell necrosis induced by chronic hypoxia plays a role in melanoma angiogenesis. J. Cancer 7, 22–31 (2016)PubMedPubMedCentralCrossRef
123.
J.J. Park, S.J. Hwang, J.-H. Park, H.-J. Lee, Chlorogenic acid inhibits hypoxia-induced angiogenesis via down-regulation of the HIF-1α/AKT pathway. Cell. Oncol. 38, 111–118 (2015)CrossRef
124.
J.-Y. Park, H.-J. Jung, I. Seo, B.K. Jha, S.-I. Suh, M.-H. Suh, W.-K. Baek, Translational suppression of HIF-1α by miconazole through the mTOR signaling pathway. Cell. Oncol. 37, 269–279 (2014)CrossRef
125.
126.
T. Kuwai, Y. Kitadai, S. Tanaka, S. Onogawa, N. Matsutani, E. Kaio, M. Ito, K. Chayama, Expression of hypoxia-inducible factor-1α is associated with tumor vascularization in human colorectal carcinoma. Int. J. Cancer 105, 176–181 (2003)PubMedCrossRef
127.
L. Huang, Z. Zhang, S. Zhang, J. Ren, R. Zhang, H. Zeng, Q. Li, G. Wu, Inhibitory action of Celastrol on hypoxia-mediated angiogenesis and metastasis via the HIF-1α pathway. Int. J. Mol. Med. 27, 407–415 (2011)PubMed
128.
C. Cursiefen, L. Chen, L.P. Borges, D. Jackson, J. Cao, C. Radziejewski, P.A. D’Amore, M.R. Dana, S.J. Wiegand, J.W. Streilein, VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment. J. Clin. Invest. 113, 1040–1050 (2004)PubMedPubMedCentralCrossRef
129.
J.C. Zampell, A. Yan, T. Avraham, S. Daluvoy, E.S. Weitman, B.J. Mehrara, HIF-1α coordinates lymphangiogenesis during wound healing and in response to inflammation. FASEB J. 26, 1027–1039 (2012)PubMedPubMedCentralCrossRef
130.
Y. Liao, W. Lu, Q. Che, T. Yang, H. Qiu, H. Zhang, X. He, J. Wang, M. Qiu, Y. Zou, W. Gu, X. Wan, SHARP1 suppresses angiogenesis of endometrial cancer by decreasing hypoxia-inducible factor-1α level. PLoS ONE 9, e99907 (2014)PubMedPubMedCentralCrossRef
131.
M.A.A. Al-Rawi, W.G. Jiang, Lymphangiogenesis and cancer metastasis. Front. Biosci. 16, 723–739 (2011)CrossRef
132.
C. Wissmann, M. Detmar, Pathways targeting tumor lymphangiogenesis. Clin. Cancer Res. 12, 6865–6868 (2006)PubMedCrossRef
133.
S. Fukunaga, K. Maeda, E. Noda, T. Inoue, K. Wada, K. Hirakawa, Association between expression of vascular endothelial growth factor C, chemokine receptor CXCR4 and lymph node metastasis In colorectal cancer. Oncology 71, 204–211 (2006)PubMedCrossRef
134.
M. Haseba, T. Tsuji, H. Yano, H. Komatsu, S. Hidaka, T. Sawai, T. Yasutake, T. Nakagoe, Y. Tagawa, Expressions of vascular endothelial growth factor (VEGF)-D and VEGF receptor-3 in colorectal cancer: relationship to lymph node metastasis. Acta Med. Nagasaki 47, 155–160 (2002)
135.
X.-B. Kang, Q.-A. Lü, W. Cui, M.-W. Zhang, L.-M. Xie, Correlations of expressions of VEGF-C, Flt-4 and survivin with metastasis of lymph nodes in colorectal carcinoma tissues. Chin. J. Cancer Prev. Treat. 14, 1232–1234 (2007)
136.
J.H. Mou, X.C. Yan, Z.P. Li, D. Wang, G.J. Duan, D.B. Xiang, H.L. Xiao, Q.H. Zhang, Characteristic and clinicopathological significance of lymphangiogenesis in colorectal cancer. Zhonghua bing li xue za zhi Chin. J. Pathol. 34, 348–352 (2005)
137.
R.B. Rebhun, A.J. Lazar, I.J. Fidler, J.E. Gershenwald, Impact of sentinel lymphadenectomy on survival in a murine model of melanoma. Clin. Exp. Metastasis 25, 191–199 (2008)PubMedCrossRef
138.
139.
S. Hirakawa, L.F. Brown, S. Kodama, K. Paavonen, K. Alitalo, M. Dietmar, VEGF-C induces lymphangiogenesis in sentinel lymph nodes promotes tumor metastasis to distant sites. Blood 109, 1010–1017 (2007)PubMedPubMedCentralCrossRef
140.
H.-J. Han, H.-B. Kim, J. Cha, J.-K. Lee, H. Youn, J.-K. Chung, S. Kim, K.-S. Soh, Primo Vessel as a novel cancer cell migration path from testis with nanoparticle-labeled and GFP expressing cancer cells. J. Acupunct. Meridian. Stud. 6, 298–305 (2013)PubMedCrossRef
141.
M.A. Islam, S.D. Thomas, K.J. Sedoris, S.P. Slone, H. Alatassi, D.M. Miller, Tumor-associated primo vascular system is derived from xenograft, not host. Exp. Mol. Pathol. 94, 84–90 (2013)PubMedCrossRef
142.
J. Lim, S. Lee, Z. Su, H.B. Kim, J.S. Yoo, K.-S. Soh, S. Kim, Y.H. Ryu, Primo vascular system accompanying a blood vessel from tumor tissue and a method to distinguish It from the blood or the lymph system. Evid. Bas. Complement. Altern. Med. Article ID 949245, 6 pages (2013)
143.
K.A. Kang, C. Maldonado, G. Perez-Aradia, P. An, K.-S. Soh, Primo Vascular System and Its Potential Role in Cancer Metastasis, in Oxygen Transport to Tissue XXXV, ed. by S. Van Huffel, G. Naulaers, A. Caicedo, D.F. Bruley, D.K. Harrison, vol. 789 (Springer Science + Business Media, LCC, New York, 2013), pp. 289–296. book part IV CrossRef
144.
J.S. Yoo, H.B. Kim, N. Won, J. Bang, S. Kim, S. Ahn, B.-C. Lee, K.-S. Soh, Evidence for an additional metastasis route: in vivo imaging of cancer cells in the primo-vascular system around tumors and organs. Mol. Imaging Biol. 13, 471–480 (2011)PubMedCrossRef
145.
N.F. Cheville (ed.), Ultrastructural Pathology the Comparative Cellular Basis of Disease, 2nd edn. (Wiley-Blackwell, Ames, 2009), pp. 1–973
Metadata
Title
The role of lymphangiogenesis and angiogenesis in tumor metastasis
Author
Roman Paduch
Publication date
01-10-2016
Publisher
Springer Netherlands
Published in
Cellular Oncology / Issue 5/2016
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-016-0281-9

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