Suppressive mechanism of salmosin, a novel disintegrin in B16 melanoma cell metastasis

We have previously reported that salmosin, a novel disintegrin, was isolate d from Korean snake (Agkistrodon halys brevicaudus) venom and significantly inhibited solid tumor growth in mice by perturbation of tumor-specific ang iogenesis via blocking alpha nu beta 3 integrin expressed on vascular endot helial cells. In this study, we investigated the functional specificity of salmosin in tumor cell metastasis. Recombinant salmosin expressed in E. col t that has the RGD sequence markedly inhibited both B16F10 melanoma cell ad hesion to the extracellular matrix proteins as well as B16F10 melanoma cell invasion through Matrigel-coated filter. The inhibition by salmosin can be caused by blocking integrins expressed on the surface of B16F10 melanoma c ells. Salmosin significantly inhibited the proliferation of B16F10 melanoma cells on the plate coated with collagen I in a dose-dependent manner. In v ivo B16F10 melanoma experimental metastasis, salmosin showed remarkable sig nificant inhibitory effect on lung tumor colonization in a concentration-de pendent manner. These results clearly demonstrate that antimetastatic activ ity of salmosin resulted from blocking the integrin-mediated adherence and alpha nu beta 3 integrin-mediated proliferation of the melanoma cells. (C) 2000 Academic Press.