Hostname: page-component-848d4c4894-cjp7w Total loading time: 0 Render date: 2024-06-27T08:27:11.087Z Has data issue: false hasContentIssue false

Crosstalk between cancer cells and blood endothelial and lymphatic endothelial cells in tumour and organ microenvironment

Published online by Cambridge University Press:  30 January 2015

Esak Lee
Affiliation:
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Niranjan B. Pandey
Affiliation:
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Aleksander S. Popel*
Affiliation:
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA Department of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
*
*Corresponding author: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 611 Traylor Research Building, 720 Rutland Avenue, Baltimore, MD 21205, USA. E-mail: apopel@jhu.edu

Abstract

Tumour and organ microenvironments are crucial for cancer progression and metastasis. Crosstalk between multiple non-malignant cell types in the microenvironments and cancer cells promotes tumour growth and metastasis. Blood and lymphatic endothelial cells (BEC and LEC) are two of the components in the microenvironments. Tumour blood vessels (BV), comprising BEC, serve as conduits for blood supply into the tumour, and are important for tumour growth as well as haematogenous tumour dissemination. Lymphatic vessels (LV), comprising LEC, which are relatively leaky compared with BV, are essential for lymphogenous tumour dissemination. In addition to describing the conventional roles of the BV and LV, we also discuss newly emerging roles of these endothelial cells: their crosstalk with cancer cells via molecules secreted by the BEC and LEC (also called angiocrine and lymphangiocrine factors). This review suggests that BEC and LEC in various microenvironments can be orchestrators of tumour progression and proposes new mechanism-based strategies to discover new therapies to supplement conventional anti-angiogenic and anti-lymphangiogenic therapies.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Hanahan, D. and Weinberg, R.A. (2011) Hallmarks of cancer: the next generation. Cell 144, 646-674 CrossRefGoogle ScholarPubMed
2. Spano, D. and Zollo, M. (2012) Tumor microenvironment: a main actor in the metastasis process. Clinical & Experimental Metastasis 29, 381-395 CrossRefGoogle ScholarPubMed
3. Langley, R.R. and Fidler, I.J. (2007) Tumor cell-organ microenvironment interactions in the pathogenesis of cancer metastasis. Endocrine Reviews 28, 297-321 CrossRefGoogle ScholarPubMed
4. Catalano, V. et al. (2013) Tumor and its microenvironment: a synergistic interplay. Seminars in Cancer Biology 23(6 Pt B), 522-532 CrossRefGoogle ScholarPubMed
5. Chen, S.T. et al. (2008) Breast tumor microenvironment: proteomics highlights the treatments targeting secretome. Journal of Proteome Research 7, 1379-1387 CrossRefGoogle ScholarPubMed
6. Whiteside, T.L. (2008) The tumor microenvironment and its role in promoting tumor growth. Oncogene 27, 5904-5912 CrossRefGoogle ScholarPubMed
7. Watnick, R.S. (2012) The role of the tumor microenvironment in regulating angiogenesis. Cold Spring Harbor Perspectives in Medicine 2, a006676CrossRefGoogle ScholarPubMed
8. Funasaka, T. and Raz, A. (2007) The role of autocrine motility factor in tumor and tumor microenvironment. Cancer and Metastasis Review 26, 725-735 CrossRefGoogle ScholarPubMed
9. Lin, Q. and Yun, Z. (2010) Impact of the hypoxic tumor microenvironment on the regulation of cancer stem cell characteristics. Cancer Biology & Therapy 9, 949-956 CrossRefGoogle ScholarPubMed
10. Gao, D. and Mittal, V. (2012) Tumor microenvironment regulates epithelial-mesenchymal transitions in metastasis. Expert Review of Anticancer Therapy 12, 857-859 CrossRefGoogle ScholarPubMed
11. Tredan, O. et al. (2007) Drug resistance and the solid tumor microenvironment. Journal of the National Cancer Institute 99, 1441-1454 CrossRefGoogle ScholarPubMed
12. Polyak, K., Haviv, I. and Campbell, I.G. (2009) Co-evolution of tumor cells and their microenvironment. Trends in Genetics 25, 30-38 CrossRefGoogle ScholarPubMed
13. Samples, J., Willis, M. and Klauber-Demore, N. (2013) Targeting angiogenesis and the tumor microenvironment. Surgical Oncology Clinics of North America 22, 629-639 CrossRefGoogle ScholarPubMed
14. Li, T. et al. (2012) Molecular regulation of lymphangiogenesis in development and tumor microenvironment. Cancer Microenvironment 5, 249-260 CrossRefGoogle ScholarPubMed
15. Cao, Y. (2005) Opinion: emerging mechanisms of tumour lymphangiogenesis and lymphatic metastasis. Nature Reviews Cancer 5, 735-743 CrossRefGoogle ScholarPubMed
16. Hirakawa, S. et al. (2003) Identification of vascular lineage-specific genes by transcriptional profiling of isolated blood vascular and lymphatic endothelial cells. American Journal of Pathology 162, 575-586 CrossRefGoogle ScholarPubMed
17. Volmer, M.W. et al. (2004) Tumor suppressor Smad4 mediates downregulation of the anti-adhesive invasion-promoting matricellular protein SPARC: landscaping activity of Smad4 as revealed by a ‘secretome’ analysis. Proteomics 4, 1324-1334 CrossRefGoogle ScholarPubMed
18. Butler, J.M., Kobayashi, H. and Rafii, S. (2010) Instructive role of the vascular niche in promoting tumour growth and tissue repair by angiocrine factors. Nature Reviews Cancer 10, 138-146 CrossRefGoogle ScholarPubMed
19. Alitalo, K. (2011) The lymphatic vasculature in disease. Nature Medicine 17, 1371-1380 CrossRefGoogle ScholarPubMed
20. Bronte, V. (2009) Myeloid-derived suppressor cells in inflammation: uncovering cell subsets with enhanced immunosuppressive functions. European Journal of Immunology 39, 2670-2672 CrossRefGoogle ScholarPubMed
21. Stearman, R.S. et al. (2008) A macrophage gene expression signature defines a field effect in the lung tumor microenvironment. Cancer Research 68, 34-43 CrossRefGoogle ScholarPubMed
22. Schoppmann, S.F. et al. (2002) Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis. American Journal of Pathology 161, 947-956 CrossRefGoogle ScholarPubMed
23. Pollard, J.W. (2009) Trophic macrophages in development and disease. Nature Reviews Immunology 9, 259-270 CrossRefGoogle ScholarPubMed
24. Banchereau, J. et al. (2000) Immunobiology of dendritic cells. Annual Review of Immunology 18, 767-811 CrossRefGoogle ScholarPubMed
25. Sozzani, S. et al. (2010) Trafficking properties of plasmacytoid dendritic cells in health and disease. Trends in Immunology 31, 270-277 CrossRefGoogle ScholarPubMed
26. Fainaru, O. et al. (2010) Tumor growth and angiogenesis are dependent on the presence of immature dendritic cells. FASEB Journal 24, 1411-1418 CrossRefGoogle ScholarPubMed
27. Pages, F. et al. (2010) Immune infiltration in human tumors: a prognostic factor that should not be ignored. Oncogene 29, 1093-1102 CrossRefGoogle Scholar
28. Galon, J., Fridman, W.H. and Pages, F. (2007) The adaptive immunologic microenvironment in colorectal cancer: a novel perspective. Cancer Research 67, 1883-1886 CrossRefGoogle ScholarPubMed
29. Valenti, R. et al. (2007) Tumor-released microvesicles as vehicles of immunosuppression. Cancer Research 67, 2912-2915 CrossRefGoogle ScholarPubMed
30. Swartz, M.A. and Lund, A.W. (2012) Lymphatic and interstitial flow in the tumour microenvironment: linking mechanobiology with immunity. Nature Reviews Cancer 12, 210-219 CrossRefGoogle ScholarPubMed
31. Madar, S., Goldstein, I. and Rotter, V. (2013) 'Cancer associated fibroblasts'–more than meets the eye. Trends in Molecular Medicine 19, 447-453 CrossRefGoogle ScholarPubMed
32. Guan, J. and Chen, J. (2013) Mesenchymal stem cells in the tumor microenvironment. Biomedical Reports 1, 517-521 CrossRefGoogle ScholarPubMed
33. Functional subsets of mesenchymal cell types in the tumor microenvironment. Cortez, E, Roswall, P, Pietras, K. Semin Cancer Biol (2014). Apr; 25:3-9. doi: 10.1016/j.semcancer.2013.12.010. Epub 2014 Jan 7.CrossRefGoogle ScholarPubMed
34. Straussman, R. et al. (2012) Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature 487, 500-504 CrossRefGoogle ScholarPubMed
35. Crawford, Y. et al. (2009) PDGF-C mediates the angiogenic and tumorigenic properties of fibroblasts associated with tumors refractory to anti-VEGF treatment. Cancer Cell 15, 21-34 CrossRefGoogle ScholarPubMed
36. Feig, C. et al. (2013) Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proceedings of the National Academy of Sciences of the United States of America 110, 20212-20217 CrossRefGoogle ScholarPubMed
37. Kraman, M. et al. (2010) Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha. Science 330, 827-830 CrossRefGoogle ScholarPubMed
38. Yu, B. et al. (2013) Stromal fibroblasts in the microenvironment of gastric carcinomas promote tumor metastasis via upregulating TAGLN expression. BMC Cell Biology 14, 17 CrossRefGoogle ScholarPubMed
39. Stracke, M.L. and Liotta, L.A. (1992) Multi-step cascade of tumor cell metastasis. In Vivo 6, 309-316 Google ScholarPubMed
40. Sahai, E. (2007) Illuminating the metastatic process. Nature Reviews Cancer 7, 737-749 CrossRefGoogle ScholarPubMed
41. Fidler, I.J., Kim, S.J. and Langley, R.R. (2007) The role of the organ microenvironment in the biology and therapy of cancer metastasis. Journal of Cellular Biochemistry 101, 927-936 CrossRefGoogle ScholarPubMed
42. Paget, S. (1989) The distribution of secondary growths in cancer of the breast. Cancer and Metastasis Review 8, 98-101 Google ScholarPubMed
43. Fidler, I.J. (1991) Orthotopic implantation of human colon carcinomas into nude mice provides a valuable model for the biology and therapy of metastasis. Cancer and Metastasis Review 10, 229-243 CrossRefGoogle ScholarPubMed
44. Araki, C. (1968) Organs with low incidence of neoplasm metastasis through blood circulation. Nihon Rinsho 26, 3217-3221 Google ScholarPubMed
45. High incidence of regional and in-transit lymph node metastasis in patients with alveolar rhabdomyosarcoma. Nishida, Y, Tsukushi, S, Urakawa, H, Sugiura, H, Nakashima, H, Yamada, Y, Ishiguro, N. Int J Clin Oncol. 2014 Jun; 19(3): 536-43. doi: 10.1007/s10147-013-0571-4. Epub 2013 Jun 4.CrossRefGoogle ScholarPubMed
46. Dos Santos, L.A. et al. (2011) Incidence of lymph node and adnexal metastasis in endometrial stromal sarcoma. Gynecologic Oncology 121, 319-322 CrossRefGoogle ScholarPubMed
47. Hirasawa, T. et al. (2009) Incidence of lymph node metastasis and the feasibility of endoscopic resection for undifferentiated-type early gastric cancer. Gastric Cancer 12, 148-152 CrossRefGoogle ScholarPubMed
48. Lu, X. et al. (2010) In vivo dynamics and distinct functions of hypoxia in primary tumor growth and organotropic metastasis of breast cancer. Cancer Research 70, 3905-3914 CrossRefGoogle ScholarPubMed
49. Rigamonti, N. and De Palma, M. (2013) A role for angiopoietin-2 in organ-specific metastasis. Cell Reports 4, 621-623 CrossRefGoogle ScholarPubMed
50. Lorusso, G. and Ruegg, C. (2012) New insights into the mechanisms of organ-specific breast cancer metastasis. Seminars in Cancer Biology 22, 226-233 CrossRefGoogle ScholarPubMed
51. Nguyen, D.X., Bos, P.D. and Massague, J. (2009) Metastasis: from dissemination to organ-specific colonization. Nature Reviews Cancer 9, 274-284 CrossRefGoogle ScholarPubMed
52. Nolan, C.P. and Abrey, L.E. (2005) Leptomeningeal metastases from leukemias and lymphomas. Cancer Treatment and Research 125, 53-69 CrossRefGoogle ScholarPubMed
53. Patel, V. et al. (2011) Decreased lymphangiogenesis and lymph node metastasis by mTOR inhibition in head and neck cancer. Cancer Research 71, 7103-7112 CrossRefGoogle ScholarPubMed
54. Allen, C.T. et al. (2013) Emerging insights into head and neck cancer metastasis. Head Neck 35, 1669-1678 CrossRefGoogle ScholarPubMed
55. Padua, D. et al. (2008) TGFbeta primes breast tumors for lung metastasis seeding through angiopoietin-like 4. Cell 133, 66-77 CrossRefGoogle ScholarPubMed
56. Gupta, G.P. et al. (2007) Mediators of vascular remodelling co-opted for sequential steps in lung metastasis. Nature 446, 765-770 CrossRefGoogle ScholarPubMed
57. Goncharova, E.A. (2013) mTOR and vascular remodeling in lung diseases: current challenges and therapeutic prospects. FASEB Journal 27, 1796-1807 CrossRefGoogle ScholarPubMed
58. Zhang, X.H. et al. (2013) Selection of bone metastasis seeds by mesenchymal signals in the primary tumor stroma. Cell 154, 1060-1073 CrossRefGoogle ScholarPubMed
59. Lee, E., Pandey, N.B. and Popel, A.S. (2014) Pre-treatment of mice with tumor-conditioned media accelerates metastasis to lymph nodes and lungs: a new spontaneous breast cancer metastasis model. Clinical & Experimental Metastasis 31, 67-79 CrossRefGoogle ScholarPubMed
60. Guidi, A.J. et al. (2000) Association of angiogenesis in lymph node metastases with outcome of breast cancer. Journal of the National Cancer Institute 92, 486-492 CrossRefGoogle ScholarPubMed
61. Edel, M.J., Harvey, J.M. and Papadimitriou, J.M. (2000) Comparison of vascularity and angiogenesis in primary invasive mammary carcinomas and in their respective axillary lymph node metastases. Clinical & Experimental Metastasis 18, 695-702 CrossRefGoogle ScholarPubMed
62. Inhibition of breast cancer growth and metastasis by a biomimetic peptide. Lee, E, Lee, SJ, Koskimaki, JE, Han, Z, Pandey, NB, Popel, AS. (2014). Sci Rep. 2014 Nov 20;4:7139. doi: 10.1038/srep07139.Google Scholar
63. Hood, J.L., San, R.S. and Wickline, S.A. (2011) Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis. Cancer Research 71, 3792-3801 CrossRefGoogle ScholarPubMed
64. Peinado, H. et al. (2012) Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nature Medicine 18, 883-891 CrossRefGoogle Scholar
65. Potente, M., Gerhardt, H. and Carmeliet, P. (2011) Basic and therapeutic aspects of angiogenesis. Cell 146, 873-887 CrossRefGoogle ScholarPubMed
66. Jain, R.K. (1999) Transport of molecules, particles, and cells in solid tumors. Annual Review of Biomedical Engineering 1, 241-263 CrossRefGoogle ScholarPubMed
67. Folkman, J. (1971) Tumor angiogenesis: therapeutic implications. New England Journal of Medicine 285, 1182-1186 Google ScholarPubMed
68. Ferrara, N. (2002) VEGF and the quest for tumour angiogenesis factors. Nature Reviews Cancer 2, 795-803 CrossRefGoogle ScholarPubMed
69. Mac Gabhann, F. et al. (2010) Systems biology of pro-angiogenic therapies targeting the VEGF system. Wiley Interdisciplinary Reviews: System Biology and Medicine 2, 694-707 Google ScholarPubMed
70. Sarmiento, R. et al. (2009) Antiangiogenic therapies in breast cancer. Current Opinion in Investigational Drugs 10, 1334-1345 Google ScholarPubMed
71. Labelle, M. and Hynes, R.O. (2012) The initial hours of metastasis: the importance of cooperative host-tumor cell interactions during hematogenous dissemination. Cancer Discovery 2, 1091-1099 CrossRefGoogle ScholarPubMed
72. Rashid, O.M. et al. (2013) Is tail vein injection a relevant breast cancer lung metastasis model? Journal of Thoracic Disease 5, 385-392 Google ScholarPubMed
73. Zadnik, P. et al. (2013) A novel animal model of human breast cancer metastasis to the spine: a pilot study using intracardiac injection and luciferase-expressing cells. Journal of Neurosurgery: Spine 18, 217-225 Google Scholar
74. Arshad, F. et al. (2010) Blood-brain barrier integrity and breast cancer metastasis to the brain. Pathology Research International 2011, 920509Google ScholarPubMed
75. Metastasis: new insights into organ-specific extravasation and metastatic niches. Irmisch, A, Huelsken, J. Exp Cell Res. 2013 Jul 1; 319(11): 1604-10. doi: 10.1016/j.yexcr.2013.02.012. Epub 2013 Feb 21.CrossRefGoogle ScholarPubMed
76. Bergers, G. and Benjamin, L.E. (2003) Tumorigenesis and the angiogenic switch. Nature Reviews Cancer 3, 401-410 CrossRefGoogle ScholarPubMed
77. Farnsworth, R.H. et al. (2011) A role for bone morphogenetic protein-4 in lymph node vascular remodeling and primary tumor growth. Cancer Research 71, 6547-6557 CrossRefGoogle ScholarPubMed
78. Lee, S.Y. et al. (2012) Changes in specialized blood vessels in lymph nodes and their role in cancer metastasis. Journal of Translational Medicine 10, 206 CrossRefGoogle ScholarPubMed
79. Von Marschall, Z. et al. (2005) Vascular endothelial growth factor-D induces lymphangiogenesis and lymphatic metastasis in models of ductal pancreatic cancer. International Journal of Oncology 27, 669-679 Google ScholarPubMed
80. Kesler, C.T. et al. (2013) Lymphatic vessels in health and disease. Wiley Interdisciplinary Reviews: System Biology and Medicine 5, 111-124 Google ScholarPubMed
81. Mohammed, R.A. et al. (2011) Lymphatic and blood vessels in basal and triple-negative breast cancers: characteristics and prognostic significance. Modern Pathology 24, 774-785 CrossRefGoogle ScholarPubMed
82. Kaipainen, A. et al. (1995) Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development. Proceedings of the National Academy of Sciences of the United States of America 92, 3566-3570 CrossRefGoogle ScholarPubMed
83. Banerji, S. et al. (1999) LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan. Journal of Cell Biology 144, 789-801 CrossRefGoogle ScholarPubMed
84. Wigle, J.T. and Oliver, G. (1999) Prox1 function is required for the development of the murine lymphatic system. Cell 98, 769-778 CrossRefGoogle ScholarPubMed
85. Yuan, L. et al. (2002) Abnormal lymphatic vessel development in neuropilin 2 mutant mice. Development 129, 4797-4806 CrossRefGoogle ScholarPubMed
86. Schacht, V. et al. (2003) T1alpha/podoplanin deficiency disrupts normal lymphatic vasculature formation and causes lymphedema. EMBO Journal 22, 3546-3556 CrossRefGoogle ScholarPubMed
87. Porter, G.J. et al. (2004) Patterns of metastatic breast carcinoma: influence of tumour histological grade. Clinical Radiology 59, 1094-1098 CrossRefGoogle ScholarPubMed
88. Perou, C.M. et al. (2000) Molecular portraits of human breast tumours. Nature 406, 747-752 CrossRefGoogle ScholarPubMed
89. Moskowitz, M. et al. (1975) Breast cancer screening. Preliminary report of 207 biopsies performed in 4, 128 volunteer screenees. Cancer 36, 2245-2250 CrossRefGoogle Scholar
90. Matsuo, S. (1974) Studies on the factors inducing metastasis of breast cancer to lymph node. I. Lymph flow in the thoracic wall. Acta Medica Okayama 28, 259-270 Google ScholarPubMed
91. Lipponen, P. et al. (2001) High stromal hyaluronan level is associated with poor differentiation and metastasis in prostate cancer. European Journal of Cancer 37, 849-856 CrossRefGoogle ScholarPubMed
92. Skobe, M. et al. (2001) Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nature Medicine 7, 192-198 CrossRefGoogle ScholarPubMed
93. Tammela, T. and Alitalo, K. (2010) Lymphangiogenesis: molecular mechanisms and future promise. Cell 140, 460-476 CrossRefGoogle ScholarPubMed
94. J Clin Oncol. 2014 May 1; 32(13): 1365-83. doi:10.1200/JCO.2013.54.1177. Epub 2014 Mar 24. Sentinel lymph node biopsy for patients with early-stage breast cancer: American Society of Clinical Oncology clinical practice guideline updateCrossRefGoogle Scholar
95. Boughey, J.C. et al. (2013) Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. Journal of American Medical Association 310, 1455-1461 CrossRefGoogle ScholarPubMed
96. Sleeman, J.P., Cady, B. and Pantel, K. (2012) The connectivity of lymphogenous and hematogenous tumor cell dissemination: biological insights and clinical implications. Clinical & Experimental Metastasis 29, 737-746 CrossRefGoogle ScholarPubMed
97. Jain, R.K. and Padera, T.P. (2002) Prevention and treatment of lymphatic metastasis by antilymphangiogenic therapy. Journal of the National Cancer Institute 94, 785-787 CrossRefGoogle ScholarPubMed
98. Achen, M.G., Mann, G.B. and Stacker, S.A. (2006) Targeting lymphangiogenesis to prevent tumour metastasis. British Journals of Cancer 94, 1355-1360 CrossRefGoogle ScholarPubMed
99. Hirakawa, S. et al. (2007) VEGF-C-induced lymphangiogenesis in sentinel lymph nodes promotes tumor metastasis to distant sites. Blood 109, 1010-1017 CrossRefGoogle ScholarPubMed
100. Harrell, M.I., Iritani, B.M. and Ruddell, A. (2007) Tumor-induced sentinel lymph node lymphangiogenesis and increased lymph flow precede melanoma metastasis. American Journal of Pathology 170, 774-786 CrossRefGoogle ScholarPubMed
101. Interaction of tumor cells and lymphatic vessels in cancer progression. Alitalo, A, Detmar, M. Oncogene. 2012 Oct 18;31(42):4499-508. doi: 10.1038/onc.2011.602.CrossRefGoogle ScholarPubMed
102. Quagliata, L. et al. (2014) Inhibition of VEGFR-3 activation in tumor-draining lymph nodes suppresses the outgrowth of lymph node metastases in the MT-450 syngeneic rat breast cancer model. Clinical & Experimental Metastasis 31, 351-365 CrossRefGoogle ScholarPubMed
103. Thomas, S.N. et al. (2014) Targeting the tumor-draining lymph node with adjuvanted nanoparticles reshapes the anti-tumor immune response. Biomaterials 35, 814-824 CrossRefGoogle ScholarPubMed
104. Lee, E. et al. (2014) Breast cancer cells condition lymphatic endothelial cells within pre-metastatic niches to promote metastasis. Nature Communications 5, 4715 CrossRefGoogle ScholarPubMed
105. Lee, E. et al. (2013) Inhibition of lymphangiogenesis and angiogenesis in breast tumor xenografts and lymph nodes by a peptide derived from transmembrane protein 45A. Neoplasia 15, 112-124 CrossRefGoogle ScholarPubMed
106. Nolan, D.J. et al. (2013) Molecular signatures of tissue-specific microvascular endothelial cell heterogeneity in organ maintenance and regeneration. Developmental Cell 26, 204-219 CrossRefGoogle ScholarPubMed
107. Kobayashi, H. et al. (2010) Angiocrine factors from Akt-activated endothelial cells balance self-renewal and differentiation of haematopoietic stem cells. Nature Cell Biology 12, 1046-1056 CrossRefGoogle ScholarPubMed
108. Ruggeri, Z.M. (2003) Von Willebrand factor, platelets and endothelial cell interactions. Journal of Thrombosis and Haemostasis 1, 1335-1342 CrossRefGoogle ScholarPubMed
109. Ding, B.S. et al. (2010) Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration. Nature 468, 310-315 CrossRefGoogle ScholarPubMed
110. Ding, B.S. et al. (2011) Endothelial-derived angiocrine signals induce and sustain regenerative lung alveolarization. Cell 147, 539-553 CrossRefGoogle ScholarPubMed
111. Weech, A.A., Goettsch, E. and Reeves, E.B. (1934) The flow and composition of lymph in relation to the formation of edema. Journal of Experimental Medicine 60, 63-84 CrossRefGoogle Scholar
112. Turner, S.G. and Barrowman, J.A. (1977) Intestinal lymph flow and lymphatic transport of protein during fat absorption. Quaterly Journal of Experimental Physiology and Cognate Medical Sciences 62, 175-180 CrossRefGoogle ScholarPubMed
113. Nykanen, A.I. et al. (2010) Targeting lymphatic vessel activation and CCL21 production by vascular endothelial growth factor receptor-3 inhibition has novel immunomodulatory and antiarteriosclerotic effects in cardiac allografts. Circulation 121, 1413-1422 CrossRefGoogle ScholarPubMed
114. Forster, R., Davalos-Misslitz, A.C. and Rot, A. (2008) CCR7 and its ligands: balancing immunity and tolerance. Nature Reviews Immunology 8, 362-371 CrossRefGoogle ScholarPubMed
115. Scandella, E. et al. (2004) CCL19/CCL21-triggered signal transduction and migration of dendritic cells requires prostaglandin E2. Blood 103, 1595-1601 CrossRefGoogle ScholarPubMed
116. Riedl, K. et al. (2003) Overexpression of CCL-21/secondary lymphoid tissue chemokine in human dendritic cells augments chemotactic activities for lymphocytes and antigen presenting cells. Molecular Cancer 2, 35 CrossRefGoogle ScholarPubMed
117. Kataru, R.P. et al. (2011) T lymphocytes negatively regulate lymph node lymphatic vessel formation. Immunity 34, 96-107 CrossRefGoogle ScholarPubMed
118. Angeli, V. et al. (2006) B cell-driven lymphangiogenesis in inflamed lymph nodes enhances dendritic cell mobilization. Immunity 24, 203-215 CrossRefGoogle ScholarPubMed
119. Brantley-Sieders, D.M. et al. (2011) Angiocrine factors modulate tumor proliferation and motility through EphA2 repression of Slit2 tumor suppressor function in endothelium. Cancer Research 71, 976-987 CrossRefGoogle ScholarPubMed
120. Hamada, J. et al. (1992) Separable growth and migration factors for large-cell lymphoma cells secreted by microvascular endothelial cells derived from target organs for metastasis. British Journal of Cancer 66, 349-354 CrossRefGoogle ScholarPubMed
121. Sadej, R. et al. (2009) CD151 regulates tumorigenesis by modulating the communication between tumor cells and endothelium. Molecular Cancer Research 7, 787-798 CrossRefGoogle ScholarPubMed
122. Warner, K.A. et al. (2008) Endothelial cells enhance tumor cell invasion through a crosstalk mediated by CXC chemokine signaling. Neoplasia 10, 131-139 CrossRefGoogle ScholarPubMed
123. Stromal endothelial cells directly influence cancer progression. Franses, JW, Baker, AB, Chitalia, VC, Edelman, ER. Sci Transl Med. 2011 Jan 19;3(66):66ra5. doi: 10.1126/scitranslmed.3001542.CrossRefGoogle ScholarPubMed
124. Heusschen, R. et al. (2010) MicroRNAs in the tumor endothelium: novel controls on the angioregulatory switchboard. Biochimica et Biophysica Acta 1805, 87-96 Google ScholarPubMed
125. Buchanan, C.F. et al. (2012) Cross-talk between endothelial and breast cancer cells regulates reciprocal expression of angiogenic factors in vitro. Journal of Cellular Biochemistry 113, 1142-1151 CrossRefGoogle ScholarPubMed
126. Am J Physiol Cell Physiol. 2014 Jul 1; 307 (1): C14–24. doi: 10.1152/ajpcell.00043.2014. Epub 2014 Apr 16. Host endothelial S1PR1 regulation of vascular permeability modulates tumor growthGoogle Scholar
127. Campos, M.S. et al. (2012) Endothelial derived factors inhibit anoikis of head and neck cancer stem cells. Oral Oncology 48, 26-32 CrossRefGoogle ScholarPubMed
128. Galan-Moya, E.M. et al. (2011) Secreted factors from brain endothelial cells maintain glioblastoma stem-like cell expansion through the mTOR pathway. EMBO Reports 12, 470-476 CrossRefGoogle ScholarPubMed
129. Krishnamurthy, S. et al. (2010) Endothelial cell-initiated signaling promotes the survival and self-renewal of cancer stem cells. Cancer Research 70, 9969-9978 CrossRefGoogle ScholarPubMed
130. Lu, J. et al. (2013) Endothelial cells promote the colorectal cancer stem cell phenotype through a soluble form of Jagged-1. Cancer Cell 23, 171-185 CrossRefGoogle ScholarPubMed
131. Kimura, C. et al. (2013) Endothelium-dependent epithelial-mesenchymal transition of tumor cells: exclusive roles of transforming growth factor beta1 and beta2. Biochimica et Biophysica Acta 1830, 4470-4481 CrossRefGoogle ScholarPubMed
132. Sigurdsson, V. et al. (2011) Endothelial induced EMT in breast epithelial cells with stem cell properties. PLoS ONE 6, e23833 CrossRefGoogle ScholarPubMed
133. Kim, M. et al. (2010) CXCR4 signaling regulates metastasis of chemoresistant melanoma cells by a lymphatic metastatic niche. Cancer Research 70, 10411-10421 CrossRefGoogle ScholarPubMed
134. Wiley, H.E. et al. (2001) Expression of CC chemokine receptor-7 and regional lymph node metastasis of B16 murine melanoma. Journal of the National Cancer Institute 93, 1638-1643 CrossRefGoogle ScholarPubMed
135. Hwang, T.L. et al. (2012) CCL7 and CCL21 overexpression in gastric cancer is associated with lymph node metastasis and poor prognosis. World Journal of Gastroenterology 18, 1249-1256 CrossRefGoogle ScholarPubMed
136. Zhuang, Z. et al. (2010) Altered phenotype of lymphatic endothelial cells induced by highly metastatic OTSCC cells contributed to the lymphatic metastasis of OTSCC cells. Cancer Science 101, 686-692 CrossRefGoogle Scholar
137. Du, Y. et al. (2013) The interaction between LYVE-1 with hyaluronan on the cell surface may play a role in the diversity of adhesion to cancer cells. PLoS ONE 8, e63463 Google ScholarPubMed
138. Paupert, J., Sounni, N.E. and Noel, A. (2011) Lymphangiogenesis in post-natal tissue remodeling: lymphatic endothelial cell connection with its environment. Molecular Aspects of Medicine 32, 146-158 CrossRefGoogle ScholarPubMed
139. Ding, Z. et al. (2005) Morphological study of the interaction between M21 melanoma and lymphatic endothelium. Lymphology 38, 87-91 Google ScholarPubMed
140. Kerjaschki, D. et al. (2011) Lipoxygenase mediates invasion of intrametastatic lymphatic vessels and propagates lymph node metastasis of human mammary carcinoma xenografts in mouse. Journal of Clinical Investigation 121, 2000-2012 CrossRefGoogle Scholar
141. Iiizumi, M., Bandyopadhyay, S. and Watabe, K. (2007) Interaction of Duffy antigen receptor for chemokines and KAI1: a critical step in metastasis suppression. Cancer Research 67, 1411-1414 CrossRefGoogle ScholarPubMed
142. Lee, E., Pandey, N.B. and Popel, A.S. (2014) Lymphatic endothelial cells support tumor growth in breast cancer. Scientific Reports 4, 5853 CrossRefGoogle ScholarPubMed
143. Swartz, M.A. et al. (2012) Tumor microenvironment complexity: emerging roles in cancer therapy. Cancer Research 72, 2473-2480 CrossRefGoogle ScholarPubMed
144. Zheng, R. et al. (2007) Significance of regional draining lymph nodes in the development of tumor immunity: implications for cancer immunotherapy. Cancer Treatment and Research 135, 223-237 CrossRefGoogle ScholarPubMed
145. Cascone, T. et al. (2011) Upregulated stromal EGFR and vascular remodeling in mouse xenograft models of angiogenesis inhibitor-resistant human lung adenocarcinoma. Journal of Clinical Investigation 121, 1313-1328 CrossRefGoogle ScholarPubMed
146. Jain, R.K. et al. (2009) Biomarkers of response and resistance to antiangiogenic therapy. Nature Reviews Clinical Oncology 6, 327-338 CrossRefGoogle ScholarPubMed
147. Kerbel, R.S. (2011) Reappraising antiangiogenic therapy for breast cancer. Breast 20(Suppl 3), S56-S60 CrossRefGoogle ScholarPubMed
148. Xu, L. et al. (2014) Sci Transl Med. 2014 Jun 25; 6(242): 242ra84. doi: 10.1126/scitranslmed.3008455. COX-2 inhibition potentiates antiangiogenic cancer therapy and prevents metastasis in preclinical models. Science Translational Medicine 6, 242 CrossRefGoogle ScholarPubMed
149. Lee, E. et al. (2011) Small peptides derived from somatotropin domain-containing proteins inhibit blood and lymphatic endothelial cell proliferation, migration, adhesion and tube formation. International Journal of Biochemistry & Cell Biology 43, 1812-1821 CrossRefGoogle ScholarPubMed
150. Koskimaki, J.E. et al. (2013) Synergy between a collagen IV mimetic peptide and a somatotropin-domain derived peptide as angiogenesis and lymphangiogenesis inhibitors. Angiogenesis 16, 159-170 CrossRefGoogle Scholar