J Cell Physiol 2008, 216:347–354.PubMedCrossRef 9. Qian CN, Berghuis B, Tsarfaty G, Bruch M, Kort EJ, Ditlev J, Tsarfaty I, Hudson E, Jackson DG, Petillo D, Chen J, Resau JH, The BT: Preparing the “”soil”": the primary tumor induces vasculature reorganization in the sentinel lymph node before the arrival of metastatic cancer cells. Cancer Res 2006, 66:10365–10376.PubMedCrossRef 10. Hirakawa S, Kodama S, Kunstfeld R, Kajiya K, Brown LF, Detmar M: VEGF-A induces tumor and sentinel lymph node lymphangiogenesis and promotes lymphatic metastasis. J Exp Med 2005, 201:1089–1099.PubMedCrossRef 11. Harrell MI, Iritani BM, Ruddell A: Tumor-induced sentinel lymph node lymphangiogenesis and increased lymph flow precede melanoma

metastasis. Am J Pathol 2007, 170:774–786.PubMedCrossRef 12. Hirakawa S, Brown LF, learn more Kodama S, Paavonen K, Alitalo K, Detmar M: VEGF-C-induced lymphangiogenesis in sentinel lymph nodes promotes tumor metastasis to distant sites. Blood 2007, 109:1010–1017.PubMedCrossRef 13. Stacker SA, Baldwin ME, Achen MG: The role of tumor lymphangiogenesis in metastatic spread. FASEB J 2002, 16:922–934.PubMedCrossRef 14. He Y, Karpanen T, Alitalo K: Role of lymphangiogenic factors in tumor metastasis. BiochimBiophys Aacta 2004, 1654:3–12. 15. 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 Birinapant in vitro (VEGFR-3) and KDR (TPX-0005 molecular weight VEGFR-2) receptor tyrosine kinases. EMBO J 1996, 15:290–298.PubMed 16. Achen MG, Jeltsch M, Kukk E, Mäkinen T, Vitali A, Wilks AF, Alitalo K, Stacker SA: 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.PubMedCrossRef 17. Mandriota SJ, Jussila L, Jeltsch M, Compagni A, Baetens D, Prevo R, Banerji S, Huarte J, Montesano R, Jackson DG, Orci L, Alitalo K, Christofori G, Pepper MS: Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumour metastasis. EMBO J 2001, 20:672–682.PubMedCrossRef 18. Stacker SA, Caesar C, Baldwin ME, Thornton GE, Williams RA, Prevo R, Jackson DG, Nishikawa S, Kubo H, Achen MG: VEGF-D promotes the metastatic spread 2-hydroxyphytanoyl-CoA lyase of tumor cells via the lymphatics. Nat Med 2001, 7:186–191.PubMedCrossRef 19. Skobe M, Hawighorst T, Jackson DG, Prevo R, Janes L, Velasco P, Riccardi L, Alitalo K, Claffey K, Detmar M: Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med 2001, 7:192–198.PubMedCrossRef 20. 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.PubMedCrossRef 21.