Tumor-induced lymphangiogenesis in cervical lymph nodes in oral melanoma-bearing 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 tumor-induced ln lymphangiogenesis controls metastasis to regional lns,we investigated cervical ln metastasis in a mouse model of oral melanoma. methods. injection of b16f10 melanoma cells into mouse tongues replicated spontaneous cervical ln metastasis. we performed histological,immunofluorescent,and histomorphometric analyses of tumor-reactive lymphadenopathy and lymphangiogenesis in tumor-associated lns. we investigated the expression of vascular endothelial growth factor (vegf)-c and its receptor,vegf receptor-3 (vegfr-3),in tumor cells and tissues,and lns by reverse transcription polymerase chain reaction and immunofluorescence. results: tumor-associated lns comprised sentinel lns (slns) before and after tumor cell invasion (tumor-bearing slns),and lns adjacent or contralateral to tumor-bearing slns. extensive lymphangiogenesis appeared in slns before evidence of metastasis. after metastasis was established in slns,both lns adjacent and contralateral to tumor-bearing slns demonstrated lymphangiogenesis. interaction between vegf-c-positive melanoma cells and vegfr-3-positive lymphatic vessels was evident in tumor-associated lns. conclusions: ln lymphangiogenesis contributes a progression of tumor metastasis from slns to other regional lns. © 2012 ozasa et al.; licensee biomed central ltd.