“…Activation of lymphatic VEGFR-3 is required for lymphangiogenesis (1,4,48), and although tumor-secreted VEGF-C is correlated with incidence of lymph node metastasis (3,7,8,49), the requirement of lymphangiogenesis for lymphatic escape of tumors has not been directly shown (11,14). Recently, it has become evident that many tumors may also express VEGFR-3 (11,(15)(16)(17)(18)(19)(20)(21)(22)(23)(24), suggesting the presence of an autocrine mechanism that might promote invasion. Furthermore, the most widely correlated factor with lymph node metastasis in human tumors has been CCR7 (28-33), a receptor required for lymphatic homing of dendritic cells (25)(26)(27).…”