tumorinduced lymphangiogenesis in cervical lymph nodes in oral melanomabearing mice background metastasis via the lymphatic system is promoted by lymphangiogenesis alterations of the lymphatic channels during the progression of metastasis to regional lymph nodes lns remain unexplored to examine whether tumorinduced ln lymphangiogenesis controls metastasis to regional lns we investigated cervical ln metastasis in a mouse model of oral melanomamethods injection of b16f10 melanoma cells into mouse tongues replicated spontaneous cervical ln metastasis we performed histological immunofluorescent and histomorphometric analyses of tumorreactive lymphadenopathy and lymphangiogenesis in tumorassociated lns we investigated the expression of vascular endothelial growth factor vegfc and its receptor vegf receptor3 vegfr3 in tumor cells and tissues and lns by reverse transcription polymerase chain reaction and immunofluorescenceresults tumorassociated lns comprised sentinel lns slns before and after tumor cell invasion tumorbearing slns and lns adjacent or contralateral to tumorbearing slns extensive lymphangiogenesis appeared in slns before evidence of metastasis after metastasis was established in slns both lns adjacent and contralateral to tumorbearing slns demonstrated lymphangiogenesis interaction between vegfcpositive melanoma cells and vegfr3positive lymphatic vessels was evident in tumorassociated lnsconclusions ln lymphangiogenesis contributes a progression of tumor metastasis from slns to other regional lns