Dynamics of lymphatic vessels during nodal metastasis of oral malignant melanoma in mice

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Using pathological and immunohistochemical approaches, we investigated whether lingual injection of B16 cells spontaneously induces cervical lymph node metastasis and whether the extent of tumor lymphangiogenesis is related to the incidence of lymph node metastasis during the local progression of a tumor. Primary tumors developed into unilateral (phase I), separated (phase II), and fused (phase III) patterns. The rate of cervical lymph node metastasis increased in both phases II and III. Intratumoral lymphatic vessel density (LVD) was significantly higher in phase III, whereas increase in peritumoral LVD started in phase II. In this study, we demonstrate the development of cervical lymph node metastasis induced by the progression of melanoma in the tongue, and provide unique evidence that an increased LVD may heighten the risk of lymph node metastasis. In particular, the peritumoral vessels may play an important role in the propensity for early metastatic spread to regional lymph nodes.