Targeting tumor lymphangiogenesis: An update

Current Medicinal Chemistry

Volumn 17, Issue 8, 2010, Pages 698-708

  Raica, M ^a   Ribatti, D ^b  

^a VICTOR BABES UNIVERSITY OF MEDICINE AND PHARMACY   (Romania)

^b UNIVERSITY OF BARI MEDICAL SCHOOL   (Italy)

Author keywords

Lymphangiogenesis; Lymphatic endothelial cell; Lymphatic microvascular density; Metastases; Tumor progression; Vascular endothelial growth factor

Indexed keywords

ANGIOPOIETIN 2; CELL MARKER; ENDOSTATIN; NEUROPILIN 2 ANTIBODY; NEUTRALIZING ANTIBODY; PODOPLANIN; SMALL INTERFERING RNA; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG; VASCULOTROPIN; VASCULOTROPIN ANTIBODY; VASCULOTROPIN C; VATALANIB;

CELL PROLIFERATION; CORRELATION ANALYSIS; GENE TARGETING; HISTOPATHOLOGY; HUMAN; INFLAMMATORY CELL; LYMPH NODE METASTASIS; LYMPH VESSEL ENDOTHELIUM; LYMPHANGIOGENESIS; MICROVASCULARIZATION; NONHUMAN; PREDICTIVE VALIDITY; PROGNOSIS; PROTEIN EXPRESSION; REGULATORY MECHANISM; REVIEW;

ENDOTHELIAL CELLS; HUMANS; LYMPHANGIOGENESIS; LYMPHATIC METASTASIS; LYMPHATIC VESSELS; NEOPLASMS; TUMOR MARKERS, BIOLOGICAL; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 77950675601     PISSN: 09298673     EISSN: None     Source Type: Journal    
DOI: 10.2174/092986710790514471     Document Type: Review

References (156)

1. Barsky, S.H.; Baker, A.; Siegal, G.P.; Togo, S.; Liotta, L.A. Use of anti-basement membrane antibodies in distinguish blood vessel capillaries from lymphatic capillaries. Am. J. Surg. Pathol., 1983, 7, 667-677.
2. Werner, J.A.; Schunk, M. Cerium-induced light-microscopic demonstration of 5′- nucleotidase activity in the lymphatic capillaries of the proximal oesophagus of the rat. Acta Histochem., 1989, 85, 15-21.
3. Ezaki, T.; Matsuno, K.; Fujii, H.; Hayashi, N.; Miyakawa, K.; Ohmori, J.; Kotani, M. A new approach for identification of rat lymphatic capillaries using a monoclonal antibody. Arch. Histol. Cytol. Suppl., 1990, 53, 77-86.
4. Sawa, Y.; Mukaida, A.; Suzuki, M.; Yoshida, S. Identification of lymphatic vessels by using a monoclonal antibody specific for the human thoracic duct. Microvasc. Res., 1997, 53, 142-149. (Pubitemid 27202430)
5. Plate, K. From angiogenesis to lymphangiogenesis. Nat. Med., 2001, 7, 151-152.
6. Pepper, M.S.; Tille, J.C.; Nisato, R.; Skobe, M. Lymphangiogenesis and tumor metastasis. Cell Tissue Res., 2003, 314, 167-177.
7. Reis-Filho, L.S.; Schmitt, F.C. Lymphangiogenesis in tumors: what do we know? Microscopy Res. Techn., 2003, 60, 171-180.
8. Hirakawa, S. From lymphangiogenesis to lymphovascular niche. Cancer Sci., 2009, doi 10.1111/j.1349-7006.2009.01142.x.
9. Banerji, S.; Ni, J.; Wang, S.X.; Clasper, S.; Su, J.; Tammi, R.; Jones, M.; Jackson, D.G. LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan. J. Cell Biol., 1999, 144, 789-801.
10. Prevo, R.; Banerji, S.; Ferguson, D.J.; Clasper, S.; Jackson, D.G. Mouse LYVE-1 is an endocytic receptor for hyaluronan in lymphatic endothelium. J. Biol. Chem., 2001, 276, 19420-19430. (Pubitemid 37411279)
11. Jackson, D.G.; Prevo, R.; Clasper, S.; Banerji, S. LYVE-1, the lymphatic system and tumor lymphangiogenesis. Trends Immunol., 2001, 22, 317-321.
12. Mouta Carreira, C.; Nasser, S.M.; di Tomaso, E.; Padera, T.P.; Boucher, Y.; Tomarev, S.I.; Jain, R.K. LYVE-1 is not restricted to the lymph vessels: expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis. Cancer Res., 2001, 61, 8079-8084.
13. Matsui, K.; Breitender-Geleff, S.; Soleiman, A.; Kowalski, H.; Kerjaschki, D. Podoplanin, a novel 43-kDa membrane protein, controls the shape of podocytes. Nephrol. Dial. Transplant. Suppl., 1999, 14, 9-11.
14. Breiteneder-Geleff, S.; Soleiman, A.; Kowalski, H.; Horvat, R.; Amann, G.; Kriehuber, E.; Diem, K.; Weninger, W.; Tschachler, E.; Alitalo, K.; Kerjaschki, D. Angiosarcomas express mixed endothelial phenotypes of blood and lymphatic capillaries: podoplanin as a specific marker for lymphatic endothelium. Am. J. Pathol., 1999, 154, 385-394. (Pubitemid 29094089)
15. Raica, M.; Cimpean, A.M.; Ribatti, D. The role of podoplanin in tumor progression and metastasis. Anticancer Res., 2008, 28, 2997-3006, 2008.
16. Schmelz, M.; Moll, R.; Kuhn, C.; Franke, W.W. Complexus adhaerentes, a new group of desmoplakin-containing junctions in endothelial cells: II. Different types of lymphatic vessels. Differentiation, 1994, 57, 97-117.
17. Sawa, Y.; Shibata, K.; Braithwaite, M.W.; Suzuki, M.; Yoshida, S. Expression of immunoglobulin superfamily members on the lymphatic endothelium of inflamed human small intestine. Microvasc. Res., 1999, 57, 100-106. (Pubitemid 29393287)
18. Oliver, G.; Detmar, M. The rediscovery of the lymphatic system: old and new insights into the development and biological function of the lymphatic vasculature. Gene Development, 2002, 16, 773-783. (Pubitemid 34280101)
19. Van der Auwera, I.; Cao, Y.; Tille, J.C.; Pepper, M.S.; Jackson, D.G.; Fox, S.B.; Harris, A.L.; Dirix, L.Y.; Vermeulen, P.B. First international consensus on the methodology of lymphangiogenesis quatification in solid human tumours. Br. J. Cancer, 2006, 95, 1611-1625.
20. Halinì, C.; Tobler, N.E.; Vigl, B.; Brown, L.F.; Detmar, M. VEGFA produced by chronically inflamed tissue induced lymphangiogenesis in draining lymph nodes. Blood, 2007, 110, 3158-3167. (Pubitemid 350106307)
21. Hirakawa, S.; Hong, Y.K.; Harvey, N.; Schacht., V.; Matsuda., K.; Libermann, T.; Detmar, M. Identification of vascular lineage-specific genes by transcriptional profiling of isolated blood vascular and lymphatic endothelial cells. Am. J. Pathol., 2003, 162, 575-586. (Pubitemid 36267864)
22. Wilting, J.; Christ, B.; Yuan, L.; Eichman, A. Cellular and molecular mechanisms of embryonic haemangiogenesis and lymphangiogenesis. Naturwissenschaften, 2003, 90, 433-448.
23. Wilting, J.; Neeff, H.; Christ, B. Embryonic lymphangiogenesis. Cell Tiss. Res., 1999, 297, 1-11.
24. Wilting, J.; Tomarev, S.I.; Christ, B.; Schweigerer, L. Lymphangioblasts in embryonic lymphangiogenesis. Lymphat. Res. Biol., 2003, 1, 33-40.
25. Joukov, V.; Pajusola, K.; Kaipainen, A.; Chilov, D.; Lahtinen, I.; Kukk, E.; Saksela, O.; Kalkkinen, N.; Alitalo, K. A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. EMBO J., 1996, 15, 290-298. (Pubitemid 26029207)
26. Achen, M.G.; Jeltsch, M.; Kukk, E.; Makinen, A.; Vitali, A.; Wilks, A.F.; Alitalo, K.; Stacker, S.A. Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (FLT4). Proc. Natl. Acad. Sci. USA, 1998, 95, 548-553.
27. Oh, S.J.; Jeltsch, M.M.; Birkenhager, R.; McCarthy, J.E.G.; Weich, H.A.; Christ, B.; Alitalo, K.; Wilting, J. VEGF and VEGF-C specific induction of angiogenesis and lymphangiogenesis in the differentiated avian chorioallantoic membrane. Dev. Biol., 1997, 188, 96-109.
28. Jeltsch, M.M.; Kaipainen, A.; Loukov, V.; Meng, X.; Lakso, M.; Rauvala, H.; Swartz, M.; Fukumura, D.; Jain, R.K.; Alitalo, K. Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science, 1997, 276, 1423-1425. (Pubitemid 27235412)
29. Karkkainen, M.J.; Haiko, P.; Sainio, K.; Partanen, J.; Taipale, J.; Petrova, T.V.; Jeltsch, M.; Jackson, D.G.; Talikka, N.; Rauvala, H.; Betsholtz, C.; Alitalo, K. Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. Nat. Immunol., 2004, 5, 74-80. (Pubitemid 38081471)
30. Hogan, B.M.; Bos, F.L.; Bussmann, J.; Witte, M.; Chi, N.C.; Duckers, H.J.; Schulte-Merker, S. Ccbe1 is required for embryonic lymphangiogenesis and venous sprouting. Nat. Genet., 2009, 41, 396-398.
31. Yuan, L.; Moyou, D.; Pardanaud, L.; Breant, C.; Karkkainen, M.J.; Alitalo, K.; Eichmann, A. Abnormal lymphatic vessel development in neuropilin 2 mutant mice. Development, 2002, 129, 4797-4806 (Pubitemid 35282411)
32. Karpanen, T.; Alitalo, K. VEGF-D: a modifier of embryonic lymphangiogenesis. Blood, 2009, 112, 1547-1548.
33. Baldwin, M.E.; Halford, M.M.; Roufail, S.; Williams, R.A.; Hibbs, M.L.; Grail, D.; Kubo, H.; Stacker, S.A.; Achen, M.G. Vascular endothelial growth factor-D is dispensable for development of lymphatic system. Mol. Cell. Biol., 2005, 25, 2441-2449. (Pubitemid 40354637)
34. Alitalo, K.; Carmeliet, P. Molecular mechanisms of lymphangiogenesis in health and disease. Cancer Cell, 2002, 1, 219-227. (Pubitemid 41039145)
35. Jussila, L.; Alitalo, K. Vascular growth factors and lymphangiogenesis. Physiol. Rev., 2002, 82, 673-700.
36. Makinen, T.; Jussila, L.; Veikkola, T.; Karpanen, T.; Catimel, B.; Nice, E.C.; Wise, L.; Mercer, A.; Kowalski, H.; Kerjaschki, D.; Stacker, S.A.; Achen, M.G.; Alitalo, K. Isolated lymphatic endothelial cells transduce growth, survival, and migratory signals via the VEGF-C/D receptor VEGFR-3. EMBO J., 2001, 20, 4762-4773. (Pubitemid 32848629)
37. Podgrabinska, S.; Braun, P.; Velasco, P.; Kloos, B.; Pepper, M.S.; Jackson, D.G.; Skobe, M. Molecular characterization of lymphatic endothelial cells. Proc. Natl. Acad. Sci. U.S.A., 2002, 99, 16069-16074. (Pubitemid 35462750)
38. Gale, N.; Thornton, G.; Hackett, S.; Renard, R.; Wang, Q.; McClain, J.; Martin, C.; Witte, C.; Witte, M.; Jackson, D.; Suri, C.; Campochiaro, P.; Wiegand, S.; Yancopoulos, G. Angiopoietin-2 is required for postnatal angiogenesis and lymphatic patterning, and only the latter role is rescued by angiopoietin 1. Dev. Cell, 2002, 3, 411-423.
39. Wigle, J.T.; Oliver, G. Prox1 function is required for the development of the murine lymphatic system. Cell, 1999, 98, 769-778. (Pubitemid 29446894)
40. Hong, Y.K.; Detmar, M. Prox 1, master regulator of the lymphatic vasculature phenotype. Cell Tissue Res., 2003, 314, 85-92. (Pubitemid 37409915)
41. Chang, L.; Kaipainen, A.; Folkman, J. Lymphangiogenesis. New mechanisms. Ann. N.Y. Acad. Sci., 2002, 979, 111-119.
42. Kubo, H.; Cao, R.; Brakenhielm, E.; Makinen, T.; Cao, Y.; Alitalo, K. Blockade of vascular endothelial growth factor receptor-3 signaling inhibits fibroblast growth factor-2-induced lymphangiogenesis in mouse cornea. Proc. Natl. Acad. Sci. U.S.A., 2002, 99, 8868-8873. (Pubitemid 34693650)
43. Achen, M.G.; Stacker, S.A. Molecular control of lymphatic metastasis. Ann. N.Y. Acad. Sci., 2008, 1131, 225-234.
44. Cao, R.; Bjorndahl, M.A.; Gallego, M.I.; Chen, S.; Religa, P.; Hansen, A.J.; Cao, Y. Hepatocyte growth factor is a lymphangiogenic factor with an indirect mechanism of action. Blood, 2006, 107, 3531-3536.
45. Cao, Y.; Bjorndahl, M.A.; Religa, P.; Clasper, S.; Garvin, S.; Galter, D.; Meister, B.; Ikomi, F.; Tritsaris, K.; Dissing, S.; Ohhashi, T.; Jackson, D.G.; Cao, Y. PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis. Cancer Cell, 2004, 6, 333-345.
46. Banzinger-Tobler, N.E.; Halin, C.; Kajiya, K.; Detmar, M. Growth hormone promotes lymphangiogenesis. Am. J. Pathol., 2008, 173, 586-597.
47. Skobe, M.; Hamberg, L.M.; Hawighorst, T.; Schirner, M.; Wolf. G.L.; Alitalo, K.; Detmar, M. Concurrent induction of lymphangiogenesis, angiogenesis, and macrophage recruitment by vascular endothelial growth factor-C in melanoma. Am. J. Pathol., 2001, 159, 893-903.
48. Mandriota, S.J.; Jussila, L.; Jeltsch, M.; Compagni, A.; Baetens, D.; Prevo, R.; Banerji, S.; Huarte, J.; Montesano, R.; Jackson, D.G.; Orci, L.; Alitalo, K.; Christofori, G.; Pepper, M.S. Vascular endothelial growth factor-C mediated lymphangiogenesis promotes tumour metastasis. EMBO J., 2001, 20, 672-682.
49. Achen, M.G.; Jeltsch, M.; Kukk, E.; Mäkinen, T.; Vitali, A.; Wilks, A.F.; Alitalo, K.; Stacker, S.A.Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk-1) and VEGF receptor 3 (Flt-4). Proc. Natl. Acad. Sci. U.S.A., 1998, 95, 548-553.
50. Stacker, S.A.; Caesar, C.; Baldwin, M.E.; Thornton, G.E.; Williams, R.A.; Prevo, R.; Jackson, D.G.; Nishikawa, S.; Kubo, H.; Achen, M.G. VEGF-D promotes the metastatic spread of tumour cells via the lymphatics. Nat. Med., 2001, 7, 186-191.
51. Veikkola, T.; Jussila, L.; Makinen, T.; Karpanen, T.; Jeltsch, M.; Petrova, T.V.; Kubo, H.; Thurston, G.; McDonald, D.M.; Achen, M.G.; Stacker, S.A., Alitalo, K. Signalling via vascular endothelial growth factor receptor-3 is sufficient for lymphangiogenesis in transgenic mice. EMBO J., 2001, 20, 1223-1231.
52. Sun, J.; Wang, Y.; Chen, Z.; Zhuo, W.; Zhu, B.; Liao, R.; Zhang, S. Detection of lymphangiogenesis in non-small cell lung cancer and its prognostic value. J. Exp. Clin. Cancer Res., 2009, 28, 21.
53. Wang, X.L.; Ai, Z.S.; Feng, J.P.; Tang, R.Y.; Chen, X.M. Expression of vascular andothelial growth factors (VEGF)-A, -C and -D and their prognostic significance and relationship with angio- and lymphangiogenesis in gastric cancer. Zhonghua Zhong Liu Za Zhi, 2008, 30, 837-843.
54. Guo, X.; Chen, Y.; Xu, Z.; Xu, Z.; Qian, Y.; Yu, X. Prognostic significance of VEGF-C expression in correlation with COX-2, lymphatic microvessel density, and clinicopathologic characteristics in human non-small cell lung cancer. Acta Biochem. Biophys. Sin., 2009, 41, 217-222.
55. Tobler, N.E.; Detmar, M. Tumor and lymph node lymphangiogenesis - impact on cancer metastasis. J. Leukoc. Biol., 2006, 80, 691-696.
56. Salven, P.; Lymboussaki, A.; Heikkila, P.; Jaaskela-Saari, H.; Enholm, B.; Aase, K.; von Euker, G.; Eriksson, U.; Alitalo, K.; Joensuu, H. Vascular endothelial growth factors VEGF-B and VEGF-C are expressed in human tumors. Am. J. Pathol., 1998, 153, 103-108.
57. Kinoshita, J.; Kitamura, K.; Kabashima, A.; Saeki, H.; Tanaka, S.; Sugimachi, K. Clinical significance of vascular endothelial growth factor- C (VEGF-C) in breast cancer. Breast Cancer Res. Treat., 2001, 66, 159-164.
58. Skobe, M.; Hamberg, L.M.; Hawighorst, T.; Schirner, M.; Wolf, G.L.; Alitalo, K.; Detmar, M. Concurrent induction of lymphangiogenesis, angiogenesis, and macrophage recruitment by vascular endothelial growth factor C in melanoma. Am. J. Pathol., 2001, 159, 889-903.
59. Chao, Y.; Jun, Z.; Jun, J.I.; Yingyan, Y.U.; Yi, Z.; Bingya, L.; Zhenggang, Z.; Haoran, Y.; Yanzhen, L. Vascular endothelial growth factor C expression in gastric carcinoma and its relationship with lymph node metastasis. Chin-Germ. J. Clin. Oncol., 2004, 3, 74-77.
60. Ishikawa, M.; Kitayama, J.; Kazama, S.; Nagawa, H. Expression of vascular endothelial growth factor (VEGF)-C in preoperatory specimens and metastatic foci of regional lymph nodes in submucosal gastric carcinoma. World J. Surg. Oncol., 2005, 3, 2.
61. Akagi, K.; Ikeda, Y.; Miyakazi, M.; Abe, T.; Kinoshita, J.; Maehara, Y.; Sugimachi, K. Vascular endothelial growth factor-C (VEGF-C) expression in human colorectal cancer tissues. Br. J. Cancer, 2000, 83, 887-891.
62. Suzuki, K.; Morita, T.; Tokue, A. Vascular endothelial growth factor-C (VEGF-C) expression predicts metastasis of transitional cell carcinoma of the bladder. Int. J. Urol., 2005, 12, 152-158.
63. Fellmer, P.T.; Sato, K.; Tanaka, R.; Okamoto, T.; Kato, Y.; Kobayashi, M.; Shibuya, M.; Obara, T. Vascular endothelial growth factor-C gene expression in papillary and follicular thyroid carcinomas. Surgery, 1999, 126, 1056-1061.
64. Li, L.; Liu, B.; Li, X.; Yang, S.; Xiao, J.; Chen, M.; Zhang, Y.; Ma, J. Vascular endothelial growth factor D and intratumoral lymphatics as independent prognostic factors in epithelial ovarian carcinoma. Anat. Rec., 2009, 292, 562-569.
65. Agarwal, B.; Saxena, R.; Morimiya, A.; Mehrotra, S.; Badve, S. Lymphangiogenesis does not occur in breast cancer. Am. J. Surg. Pathol., 2005, 29, 1449-1455.
66. Thiele, W.; Sleman J.P. Tumor-induced lymphangiogenesis: a target for cancer therapy ? J. Biotechnol., 2006; 124, 224-323
67. Ji, R.C.; Eshita, Y.; Kato, S. Investigation of intratumoural and peritumoral lymphatics expressed by podoplanin and LYVE-1 in the hybridoma-induced tumours. Int. J. Exp. Path., 2007, 88, 257-270.
68. Alitalo, K.; Tammela, T.; Petrova, T.V. Lymphangiogenesis in development and human disease. Nat. Insights, 2005, 438, 946-953.
69. Ji, R.C. Lymphatic endothelial cells, tumor lymphangiogenesis and metastasis: new insights into intratumoral and peritumoral lymphatics. Cancer Metastasis Rev., 2006, 25, 677-694.
70. Gombos, Z.; Xu, X.; Chu, C.S.; Zhang, P.; Acs, G. Peritumoral lymphatic vessel density and vascular endothelial growth factor C expression in early stage squamous cell carcinoma of the uterine cervix. Clin. Cancer Res., 2005, 11, 8367-8371.
71. Renyi-Vamos, F.; Tovari, J.; Fillinger, J.; Timar, J.; Paku, S.; Kenessey, I.; Ostoros, G.; Agocs, L.; Soltesz, B.; Dome, B. Lymphangiogenesis correlates with lymph node metastasis, prognosis, and angiogenic phenotype in human non-small cell lung cancer. Clin. Cancer Res., 2005, 11, 7344-7353.
72. Adachi, Y.; Nakamura, H.; Kitamura, Y.; Taniguchi, Y.; Araki, K.; Shomori, K.; Horie, Y.; Kurozawa, Y.; Ito, H.; Hayashi, K. Lymphatic vessel density in pulmonary adenocarcinoma immunohistochemically evaluated with anti-podoplanin or anti-D2-40 antibody is correlated with lymphatic invasion or lymph node metastases. Pathol. Intern., 2007, 57, 171-177.
73. Koukourakis, M.I.; Giatromanolaki, A.; Sivridis, E.; Simopoulos, C.; Gatter, K.C.; Harris, A.L.; Jackson, D.G. LYVE-1 immunohistochemical assessment of lymphangiogenesis in endometrial and lung cancer. J. Clin. Pathol., 2005, 58, 202-206.
74. Jain, R.K.; Fenton, B.T. Intratumoral lymphatic vessels: a case of mistaken identity or malfunction? J. Natl. Cancer Inst., 2002, 94, 417-421.
75. Beasley, N.J.P.; Prevo, R.; Banerji, S.; Leek, D.R.; Moore, J.; van Trappen, Ph.; Cox, G.; Harris, A.L.; Jackson, D.G. Intratumoral lymphangiogenesis and metastasis in head and neck cancer. Cancer Res., 2002, 62, 1315-1320.
76. Dadras, S.S.; Lange-Asschenfeldt, B.; Velasco, P.; Nguyen, L.; Vora, A.; Muzikansky, A.; Jahnke, K.; Hauschild, A.; Hirakawa, S.; Mihm, M.C.; Detmar, M. Tumor lymphangiogenesis predicts melanoma metastasis to sentinel lymph nodes. Mod. Pathol., 2005, 18, 1232-1242. (Pubitemid 43079923)
77. Raica, M.; Ribatti, D.; Mogoanta, L.; Cimpean, A.M.; Ioanovici, S. Podoplanin expression in advanced-stage gastric carcinoma and prognostic value of lymphatic microvessel density. Neoplasma, 2008, 55, 454-459.
78. Sipos, B.; Klapper, W.; Kruse, M.L.; Kalthoff, H.; Kerjanschki, D.; Kloppel, G. Expression of lymphangiogenic factors and evidence of intratumoral lymphangiogenesis in pancreatic endocrine tumors. Am. J. Pathol., 2004, 165, 1187-1197.
79. Inoue, A.; Moriya, H.; Katada, N.; Tanabe, S.; Kobayashi, N.; Watanabe, M.; Okayasu, I.; Ohbu, M. Intratumoral lymphangiogenesis of esophageal squamous cell carcinoma and relationship with regulatory factors and prognosis. Pathol. Int., 2008, 58, 611-619.
80. Vleugel, M.M.; Bos, R.; van der Groep, P.; Greijer, A.E.; Shvarts, A.; Stel, H.V.; van der Wall, E.; van Diest, P.J. Lack of lymphangiogenesis during breast carcinogenesis. J. Clin. Pathol., 2004, 57, 746-751.
81. Williams, C.S.M.; Leek, R.D.; Robson, A.M.; Banerji, S.; Prevo, R.; Harris, A.L.; Jackson, D.G. Absence of lymphangiogenesis and intratumoural lymph vessels in human metastatic breast cancer. J. Pathol., 2003, 200, 195-206.
82. Schoppmann, S.F.; Mayer, G.; Aumayr, K.; Taucher, S.; Geleff, S.; Rudas, M.; Kubista, E.; Hausmaninger, H.; Samonigg, H.; Gnant, M.; Jakesz, R.; Horvat, R. Austrian Breast and Colorectal Cancer Study Group. Prognostic value of lymphangiogenesis and lymphovascular invasion in breast cancer. Ann. Surg., 2004, 240, 306-312.
83. Zhang, S.; Yu, H.; Zhang, L. Clinical implications of increased lymph vessel density in the lymphatic metastasis of early-stage invasive cervical carcinoma: a clinical immunohistochemical method study. BMC Cancer, 2009, 9, 64.
84. Liang, P.; Hong, J.W.; Ubukata, H.; Liu, H.-R.; Watanabe, Y.; Katano, M.; Motohashi, G.; Kasuga, T.; Nakada, I.; Tabuchi, T. Increased density and diameter of lymphatic microvessel correlate with lymph node metastases in early stage invasive colorectal carcinoma. Virchows Arch., 2006, 448, 570-575.
85. Braun, M.; Flucke, U.; Debald, M.; Walgenbach-Bruenagel, G.; Walgenbach, K.J.; Höller, T.; Pölcher, M.; Wolfgarten, M.; Sauerwald, A.; Keyver-Paik, M.; Kühr, M.; Büttner, R.; Kuhn, W. Detection of lymphovascular invasion in early breast cancer by D2-40 (podoplanin) : a clinically useful predictor for axillary lymph node metastases. Breast Cancer Res. Treat., 2008, 112, 503-511.
86. Marinho, V.F.Z.; Metze, K.; Sanches, F.S.F.; Rocha, G.F.S.; Gobbi, H. Lymph vascular invasion in invasive mammary carcinomas identified by the endothelial lymphatic marker D2-40 is associated with other indicators of poor prognosis. BMC Cancer, 2008, 8, 64.
87. Niakosari, F.; Kahn, H.J.; McCready, D.; Ghazarian, D.; Rotstein, L.E.; Marks, A.; Kiss, A.; From, L. Lymphatic invasion identified by monoclonal antibody D2-40, younger age, and ulceration: predictors of sentinel lymph node involvement in primary cutaneous melanoma. Arch. Dermatol., 2008, 144, 462-467.
88. Schmidt, C.R.; Panageas, K.S.; Coit, D.G.; Patel, A.; Brady, M.S. An increased number of sentinel lymph nodes is associated with advanced Breslow depth and lymphovascular invasion in patients with primary melanoma. Ann. Surg. Oncol., 2009, 16, 948-952.
89. Volker, H.U.; Scheich, M.; Nowack, I.; Metzger, A.; Haubitz, I.; Puppe, B.; Hagen, R.; Muller-Hermelinck, H.K.; Volter, C. Lymphangiosis carcinomatosa in squamous cell carcinomas of larynx and hypopharynx - value of conventional evaluation and additional immunohistochemical staining of D2-40. World J. Surg. Oncol., 2009, 7, 25.
90. Ohno, F.; Nakanishi, H.; Abe, A.; Seki, Y.; Kinoshita, A.; Hasegawa, Y.; Tatematsu, M.; Kurita, K. Regional difference in intratumoral lymphangiogenesis of oral squamous cell carcinoma evaluated by immunohistochemistry using D2-40 and podoplanin antibody: an analysis in comparison with angiogenesis. J. Oral Pathol. Med., 2007, 36, 281-289.
91. Gao, P.; Zhou, G.Y.; Zheng, Q.H.; Su, Z.X.; Zhang, T.G.; Xiang, L.; Wang, Y.; Zhang, S.L.; Hu, K. Lymphangiogenesis in gastric carcinoma correlates with prognosis. J. Pathol., 2009, 218, 192-200.
92. Omachi, T.; Kawai, Y.; Mizuno, R.; Nomiyama, T.; Miyagawa, S.; Ohhashi, T.; Nakayama, J. Immunohistochemical demonstration of proliferating lymphatic vessels in colorectal carcinoma and its clinicopathological significance. Cancer Lett., 2007, 246, 167-172.
93. Van der Auwera, I.; van der Eynden, G.G.; Colpaert, C.G.; van Laere, S.J.; van Dam, P.; van Marck, E.A.; Dirix, L.Y.; Vermeulen, P.B. Tumor lymphangiogenesis in inflammatory breast carcinoma: a histomorphometric study. Clin. Cancer Res., 2005, 11, 7637-7642.
94. Mohammed, R.A.A.; Ellis, I.O.; Elsheikh, S.; Paish, E.C.; Martin, S.G. Lymphatic and angiogenic characteristics in breast cancer: morphometric analysis and prognostic implications. Breast Cancer Res. Treat., 2009, 113, 261-274.
95. Baldewijns, M.M.; Roskams, T.; Ballet, V.; Van den Eynden, G.G.; Van Laere, S.J.; Van der Auwera, I.; Lerut, E.; De Bruine, A.P.; Thijssen, V.L.; Vermeulen, P.B.; Van Poppel, H. A low frequency of lymph node metastasis in clear-cell renal cell carcinoma is related to low lymphangiogenic activity. BJU Intern., 2009, doi 10.1111/j.1464-410X.2008.08272.x
96. Stacker, S.A.; Caesar, C.; Baldwin, M.E.; Thronton, G.E.; Williams, R.A.; Prevo, R.; Jackson, D.G.; Nishikawa, S.; Kubo, H.; Achen, M.G. VEGF-D promotes the metastatic spread of tumor cells via the lymphatics. Nat. Med., 2001, 7, 186-191.
97. Arigami, T.; Natsugoe, S.; Uenosono, Y.; Yanagita, S.; Ehi, K.; Arima, H.; Mataki, Y.; Nakajo, A.; Ishigami, S.; Aikou, T. Vascular endothelial growth factor-C and -D expression correlates with lymph node micrometastasis in pNo early gastric cancer. J. Surg. Oncol., 2009, 99, 148-153.
98. Bonsib, S.M. Renal lymphatics and lymphatic involvement in sinus vein invasive (pT3b) clear cell renal cell carcinoma: a study of 40 cases. Mod. Pathol., 2006, 19, 746-753.
99. Hirakawa, S.; Kodama, S.; Kunstfeld, R.; Kajiya, K.; Brown, L.F.; Detmar, M. VEGF-A induces tumor and sentinel lymph node lymphangiogenesis and promotes lymphatic metastasis. J. Exp. Med., 2005, 201, 1089-1099.
100. Hirakawa, S.; Brown, L.F.; Kodama, S.; Paavonen, K.; Alitalo, K.; Detmar, M. VEGF-C-induced lymphangiogenesis in sentinel lymph node promotes metastasis to distant sites. Blood, 2007, 109, 1010-1017.
101. Van den Eynden, G.G.; Vandenberghe, M.K.; van Dam, P.J.H.; Colpaert, C.G.; van Dam, P.; Dirix, L.Y.; Vermeulen, P.B.; Van Marck, E.A. Increased sentinel lymph node lymphangiogenesis is associated with nonsentinel axillary lymph node involvement in breast cancer patients with a positive sentinel lymph node. Clin. Cancer Res., 2007, 13, 5391-5397.
102. Kawai, H.; Minamiya, Y.; Ito, M.; Saito, H.; Ogawa, J. VEGF121 promotes lymphangiogenesis in the sentinel lymph node of nonsmall cell lung carcinoma patients. Lung Cancer, 2008, 59, 41-47.
103. Kaifi, J.T.; Yekebas, E.F.; Schurr, P.; Obonyo, D.; Wachowiak, R.; Busch, P.; Heinecke, A.; Pantel, K.; Izbicki J.R. Tumor cell homing to lymph nodes and bone marrow and CXCR4 expression in esophageal cancer. J. Natl. Cancer. Inst., 2005, 97, 1840-1847.
104. Kerjanschki, D.; Regele, H.M.; Moosberger, I.; Nagy-Bojarski, K.; Watshinger, B.; Soleiman, A.; Birner, P.; Krieger, S.; Hovorka, A.; Silberhumer, G.; Laakkonen, P.; Petrova, T.; Langer, B.; Raab, I. Lymphatic neoangiogenesis in human kidney transplant is associated with immunologically active lymphocytic infiltrates. J. Am. Soc. Nephrol., 2004, 15, 603-612.
105. Angeli, V.; Ginhoux, F.; Llodrà, J; Quemeneur, L.; Frenette, P.S.; Skobe, M.; Jessberger, R.; Merad, M.; Randolph, G.J. B cell-driven lymphangiogenesis in inflamed lymph nodes enhances dendritic cell mobilization. Immunity, 2006, 24, 203-215.
106. Halin, C.; Detmar, M. An unexpected connection: lymph node lymphangiogenesis and dendritic cell migration. Immunity, 2006, 24, 129-131.
107. Hamrah, P.; Chen, L.; Zhang, Q.; Dana, M.R. Novel expression of vascular endothelial growth factor receptor (VEGFR)-3 and VEGFC on corneal dendritic cells. Am. J. Pathol., 2003, 163, 57-68.
108. Chen, L.; Hamrah, P.; Cursfien, C., Zhang, Q.; Pytpwski, B.; Streilein, J.W.; Dana, M.R. Vascular endothelial growth factor receptor-3 mediates induction of corneal alloimmunity. Nat. Med., 2004, 10, 813-815.
109. Hagemann, T.; Biswas, S.K.; Lawrence, T.; Sica, A.; Lewis, C.E. Regulation of macrophage function in tumors: the multifaceted role of NF-kappa B. Blood, 2009, 113, 3139-3146.
110. Schoppmann, S.F.; Birner, P.; Stockl, J.; Kalt, R.; Ullrich, R.; Caucig, C.; Kriehuber, E.; Nagy, K.; Alitalo, K.; Kerjanschki, D. Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis. Am. J. Pathol., 2002, 161, 947-956.
111. Cursiefen, C.; Chen, L.; Borges, L.P.; Jackson, D.; Cao, J.; Radzejewski, C.; D'Amore, P.; Reza Dana, M.; Woegand, S.J.; Streilein, J.W. VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment. J. Clin. Invest., 2004, 113, 1040-1050.
112. Maruyama, K.; Ii, M.; Cursiefen, C.; Jackson, D.G.; Keino, H.; Tomita, M.; Van Rooijen, N.; Takenaka, H.; D'Amore, P.A.; Stein-Streilein, J.; Losordo, D.W.; Streilein, J.W. Inflammation-induced lymphangiogenesis in the cornea arises from CD11b-positive macrophages. J. Clin. Invest., 2005, 115, 2363-2372.
113. Detoraki, A.; Staiano, R.I.; Granata, F.; Giannattasio, G.; Prevete, N.; de Paulis, A.; Ribatti, D.; Genovese, A.; Triggiani, M.; Marone, G. Vascular endothelial growth factors synthesized by human lung mast cells exert angiogenic effects. J. Allergy Clin. Immunol., 2009, 123, 1142-1149.
114. Fenzl, A.; Schopmann, S.F.; Geleff, S.; Birner, P.; Wrba, F.; Herberger, B.; Teleky, B.; Herbst, F.; Kuhrer, I.; Jakesz, R.; Langle, F. Vascular endothelial growth factor-C expression and lymphangiogenesis in colorectal cancer. Eur. Surg., 2006, 38, 149-154.
115. Choi, W.W.L.; Lewis, M.M.; Lawson, D.; Yin-Goen, Q.; Birdsong, G.G.; Cotsonis, G.A.; Cohen, C.; Young, A.N. Angiogenic and lymphangiogenic microvessel density in breast carcinoma: correlation with clinicopathologic parameters and VEGF-family gene expression. Mod. Pathol., 2005, 18, 143-152.
116. Schoppmann, S.F.; Fenzl, A.; Schindl, M.; Bachleitner-Hofmann, T.; Nagy, K.; Gnant, M.; Horvat, R.; Jakesz, R.; Birner, P. Hypoxia inducible factor-1α correlates with VEGF-C expression and lymphangiogenesis in breast cancer. Breast Cancer Res. Treat., 2006, 99, 135-141.
117. Donoghue, J.F.; Lederman, F.L.; Susil, B.J.; Rogers, P.A.W. Lymphangiogenesis of normal endometrium and endometrial adenocarcinoma. Hum. Reprod., 2007, 22, 1705-1713.
118. Thelen, A.; Jonas, S.; Benckert, C.; Weichert, W,; Schott, E.; Bötcher, C.; Dietz, E.; Wiedenmann, B.; Neuhaus, P.; Scholz, A. Tumor-associated lymphangiogenesis correlates with prognosis after resection of human hepatocellular carcinoma. Ann. Surg. Oncol., 2009, 16, 1222-1231.
119. Wobster, M.; Siedel, C.; Schrama, D.; Brocker, E.B.; Becker, J.C.; Vetter-Kauczok, C.S. Expression pattern of the lymphatic and vascular markers VEGFR-3 and CD31 does not predict regional lymph node metastasis in cutaneous melanoma. Arch. Dermatol. Res., 2006, 297, 352-357.
120. Sahni, D.; Robson, A.; Orchard, G.; Szydlo, R.; Evans, A.V.; Russell-Jones, R. The use of LYVE-1 antibody for detecting lymphatic involvement in patients with malignant melanoma of known sentinel node status. J. Clin. Pathol., 2005, 58, 715-721.
121. Shields, J.D.; Borsetti, M.; Rigby, H.; Harper, S.J.; Mortimer, P.S.; Levick, J.R.; Orlando, A.; Bates, D.O. Lymphatic density and metastatic spread in human malignant melanoma. Br. J. Cancer, 2004, 90, 693-700.
122. Massi, D.; Puig, S.; Franchi, A.; Malvehy, J.; Vidal-Sicard, S.; Gonzalez-Cao, M.; Baroni, G.; Ketabchi, S.; Palou, J.; Santucci, M. Tumour lymphangiogenesis is a possible predictor of sentinel lymph node status in cutaneous melanoma: a case-control study. J. Clin. Pathol., 2006, 59, 166-173.
123. Nakamura, Y.; Yasuoka, H.; Tsujimoto, M.; Kurozumi, K.; Nakahara, M.; Nakao, K.; Kakudo, K. Importance of lymph vessels in gastric cancer: a prognostic indicator in general and a predictor for lymph node metastasis in early stage cancer. J. Clin. Pathol., 2006, 59, 77-82.
124. Matsumoto, K.; Nakayama, Y.; Inoue, Y.; Minagawa, N.; Katsuki, T.; Shibao, K.; Tsurudome, Y.; Hirata, K.; Nagata, N.; Itoh, H. Lymphatic microvessel density is an independent prognostic factor in colorectal cancer. Dis. Colon Rectum, 2006, 50, 308-314.
125. Kaneko, I.; Tanaka, S.; Oka, S.; Kawamura, T.; Hiyama, T.; Ito, M.; Yoshihara, M.; Shimamoto, F.; Chayama, K. Lymphatic vessel density at the site of deepest penetration as a predictor of lymph node metastasis in submucosal colorectal cancer. Dis. Colon Rectum, 2006, 50, 13-21.
126. Chen, W.; Chen, M.; Liao, Z.; Wang, Y.; Zhan, O.; Cai, G. Lymphatic vessel density as predictive marker for the local recurrence of rectal cancer. Dis. Colon Rectum, 2009, 52, 513-519.
127. Miyahara, M.; Tanuma, J.; Sugihara, K.; Semba, I. Tumor lymphangiogenesis correlates with lymph node metastasis and clinicopathologic parameters in oral squamous cell carcinoma. Cancer, 2007, 110, 1287-1294.
128. Sugiura, T.; Inoue, Y.; Matsuki, R.; Ishii, K.; Takahashi, M.; Abe, M.; Shirasuna, K. VEGF-C and VEGF-D expression is correlated with lymphatic vessel density and lymph node metastasis in oral squamous cell carcinoma: implications for use as a prognostic marker. Intern. J. Oncol., 2009, 34, 673-680.
129. Schacht, V.; Dadras, S.S.; Johnson, L.A.; Jackson, D.G.; Hong, Y.K.; Detmar, M. Up-regulation of the lymphatic marker podoplanin, a mucin-type glycoprotein, in human squamous cell carcinoma and germ cell tumors. Am. J. Pathol., 2005, 166, 913-921.
130. Wicki, A.; Lehembre, F.; Wick, N.; Hantusch, B.; Kerjaschki, D.; Christofori, G. Tumor invasion in the absence of epithelial-mesenchymal transition: podoplanin-mediated remodeling of the actin cytoskeleton. Cancer Cell, 2006, 9, 261-272.
131. Kato, Y.; Kaneko, M.K.; Kuno, A.; Uchiyama, N.; Amano, K.; Chiba, Y.; Hasegawa, Y.; Hirabayashi, M.; Narimatsu, H.; Mishima, K.; Osawa, M. Inhibition of tumor cell-induced platelet aggregation using a novel anti-podoplanin antibody reacting with its platelet-aggregation-stimulating domain. Biochem. Biophys. Res. Commun., 2006, 349, 1301-1307.
132. Kimura, N.; Kimura, I. Podoplanin as a marker for mesothelioma. Pathol. Int., 2005, 55, 83-86.
133. Kato, Y.; Kaneko, M.; Sata, M.; Fujita, N.; Tsuruo, T.; Osawa, M. Enhanced expression of Aggrus (T1α/podoplanin), a platelet aggregation-inducing factor in lung squamous cell carcinoma. Tumor Biol., 2005, 26, 195-200.
134. Mishima, K.; Kato, Y.; Kaneko, M.K.; Nakazawa, Y.; Kunita, A.; Fujita, N.; Tsuruo, T.; Nishikawa, R.; Hirose, T.; Matsutani, M. Podoplanin expression in primary central nervous system germ cell tumors: a useful histological marker for the diagnosis of germinoma. Acta Neuropathol., 2006, 111, 563-568.
135. Fukunaga, M. Expression of D2-40 in lymphatic endothelium of normal tissues and in vascular tumours. Histopathology, 2005, 46, 396-402.
136. Chuang, W.Y.; Yeh, C.J.; Wu, Y.C.; Chao, Y.K.; Liu, Y.H.; Tseng, C.K.; Chang, H.K.; Liu, H.P.; Hsueh, C. Tumor cell expression of podoplanin correlates with nodal metastasis in esophageal squamous cell carcinoma. Histol. Histopathol., 2009, 24, 1021-1027.
137. Mishima, K.; Kato, Y.; Kaneko, M.K.; Nishikawa, R.; Hirose, T.; Matsutani, M. Increased expression of podoplanin in malignant astrocytic tumors as a novel molecular marker of malignant progression. Acta Neuropathol., 2006, 111, 483-488.
138. Nakamura, Y.; Kanemura, Y.; Yamada, T.; Sugita, Y.; Higaki, K.; Yamamoto, M.; Takahashi, M.; Yamasaki, M. D2-40 antibody immunoreactivity in developing human brain, brain tumors and cultured neural cells. Mod. Pathol., 2006, 19, 974-985.
139. Kato, Y.; Kaneko, M.K.; Kunita, A.; Ito, H.; Kameyama, A.; Ogasawara, S.; Matsuura, N.; Hasegawa, Y.; Inoue, K.; Inoue, O.; Ozaki, Y.; Narimatsu, H. Molecular analysis of the pathophysiological binding of the platelet aggregation-inducing factor podoplanin to the C-type lectin-like receptor CLEC-2. Cancer Sci., 2007, 3, 1-8. (Pubitemid 350239031)
140. Suzuki-Inoue, K.; Kato, Y.; Inoue, O.; Kaneko, M.K.; Mishima, K.; Yatomi,
141. Wicki, A.; Christofori, G. The potential role of podoplanin in tumour invasion. Br. J. Cancer, 2007, 96, 1-5. (Pubitemid 46094630)
142. He, Y.; Rajantie, I.; Pajusola, K.; Jeltsch, M.; Holopainen, T.; Yla-Herttuala, S.; Harding, T.; Jooss, K.; Takahashi, T.; Alitalo, K. Vascular endothelial cell growth factor receptor 3-mediated activation of lymphatic endothelium is crucial for tumor cell entry and spread via lymphatic vessels. Cancer Res., 2005, 65, 4739-4746. (Pubitemid 40740810)
143. Lin, J.; Lalani, A.S.; Harding, T.C.; Gonzalez, M.; Wu, W.W.; Luan, B.; Tu, G.H.; Koprivnikar, K.; VanRoey, M.J.; He, Y.; Alitalo, K.; Jooss, K. Inhibition of lymphogenous metastasis using adeno-associated virus-mediated gene transfer of a soluble VEGFR-3 decoy receptor. Cancer Res., 2005, 65, 6901-6909. (Pubitemid 41060729)
144. Kubo, H.; Fujiwara, T.; Jussila, L.; Hashi, H.; Ogawa, M.; Shimizu, K.; Awane, M.; Sakai, Y.; Takabayashi, A.; Alitalo, K.; Yamaoka, Y.; Nishikawa, S.I. Involvement of vascular endothelial growth factor receptor-3 in maintenance of integrity of endothelial cell lining during tumor angiogenesis. Blood, 2000, 96, 546-553.
145. Makinen, T.; Jussila, L.; Veikkola, T.; Karpanen, T.; Kettunen, M.I.; Pulkkane, K.J.; Kauppinen, R., Jackson, D.G.; Kubo, H.; Nishikawa, S.; Ylä-Herttuala, S.; Alitalo, K. Inhibition of lymphangiogenesis with resulting lymphedema in transgenic mice expressing soluble VEGF receptor-3. Nat. Med., 2001, 2, 199-205. (Pubitemid 32148487)
146. He, Y.; Kozaki, K.; Karpanen, T.; Koshikawa, K.; Yla-Herttuala, S.; Takahashi, T.; Alitalo, K. Supression of tumor lymphangiogenesis and lymph node metastasis by blocking vascular endothelial growth factor receptor 3 signalling. J. Natl. Cancer Inst., 2002, 94, 819-825. (Pubitemid 34705053)
147. Krishnan, J.; Kirkin, V.; Steffen, A.; Hegen, M.; Weih, D.; Tomarev, S.; Wilting, J.; Sleeman, J.P. Differential in vivo and in vitro expression of vascular endothelial growth factor (VEGF)-C and VEGF-D in tumors and its relationship to lymphatic metastasis in immunocompromized rats. Cancer Res., 2003, 63, 713-722.
148. Karpanen, T.; Egeblad, M.; Karkkainen, M.J.; Kubo, H.; Yla-Herttuala, S.; Jaattela, M.; Alitalo, K. Vascular endothelial growth factor C promotes tumor lymphangiogenesis and intralymphatic tumor growth. Cancer Res., 2001, 61, 1786-1790. (Pubitemid 32691984)
149. Saintigny, P.; Morere, J.F.; Breau, J.L.; Bernaudin, J.F.; Kraemer, M. Lymph node metastasis as a new target for cancer treatment. Targ. Oncol., 2007, 2, 49-57.
150. Schomber, T.; Zumsteg, A.; Strittmatter, K.; Crnic, I.; Antoniadis, H.; Littlewood-Evans, A.; Wood, J.; Christofori, G. Differential effects of the vascular endothelial growth factor receptor inihibitor PTK787/ZK222584 on tumor angiogenesis and lymphangiogenesis. Mol. Cancer Ther., 2009, 8, 55-63.
151. He, X.W.; Liu, T.; Xiao, Y.; Feng, Y.L.; Cheng, D.J.; Tingting, G.; Zhang, L.; Zhang, Y.; Chen, Y.X.; Tingting, G.; Zhang, L. Vascular endothelial growth factor-C siRNA delivered via calcium carbonate nanoparticle effectively inhibits lymphangiogenesis and growth of colorectal cancer in vivo. Cancer Biother. Radiopharm., 2009, 24, 249-259.
152. Guo, B.; Zhang, Y.; Luo, G.; Li, L.; Zhang, G. Lentivirus-mediated small interfering RNA targeting VEGF-C inhibited tumor lymphangiogenesis and growth in breast carcinoma. Anat. Rec., 2009, 292, 633-639.
153. Bagri, A.; Tessier-Lavigne, M.; Watts, R.J. Neuropilins in tumor biology. Clin. Cancer Res., 2009, 15, 1860-1864.
154. Whitehurst, B.; Flister, M.J.; Bagaitkar, J.; Volk, L.; Bivens, C.M.; Pickett, B.; Castro-Rivera, E.; Brekken, R.A.; Gerard, R.D.; Ran, S. Anti-VEGF-A therapy reduces lymphatic vessel density and expression of VEGFR-3 in an orthotopic breast tumor model. Int. J. Cancer, 2007, 121, 2181-2191. (Pubitemid 47585596)
155. Fukumoto, S.; Morifuji, M.; Katakura, Y.; Ohishi, M.; Nakamura, S. Endostatin inhibits lymph node metastasis by a down-regulation of the vascular endothelial growth factor C expression in tumor cells. Clin. Exp. Metastasis, 2005, 22, 31-38. (Pubitemid 41185859)
156. Kobayashi, S.; Kishimoto, T.; Kamata, S.; Otsuka, M.; Miyazaki, M.; Ishikura, H. Rapamycin, a specific inhibitor of the mammalian target rapamycin, suppresses lymphangiogenesis and lymphatic metastasis. Cancer Sci., 2007, 98, 726-733.