Laminin-421 produced by lymphatic endothelial cells induces chemotaxis for human melanoma cells

Here, the authors investigate the molecular mechanism of lymphatic metastasis. They examined the influence of interactions between normal lymphatic endothelial cells (LECs) and melanoma cells on cell migration. LEC conditioned medium (LEC-CM) contained chemotactic and chemokinetic activities for human melanoma cell lines. The chemotactic activity of LEC-CM was abolished by immunodepletion with anti-laminin-1 antibody. And immunoprecipitation and Western blot analyses revealed that LEC-CM contained laminin a4 and 5, b1 and 2, and c1, corresponding to isoforms -521, -511, -421 and -411. When melanoma C8161 cells were treated with function-blocking antibodies to integrin a3 or a6, their chemotactic responses to LEC-CM were markedly reduced. Furthermore, the knock-down of tetraspanin CD151 weakened the chemotactic responses of C8161 and MeWo cells to LEC-CM. These data suggest that laminin secreted by LEC possibly facilitates lymphatic metastasis through the induction of chemotaxis of melanoma cells.