Inhibition of melanoma cell motility by the snake venom disintegrin eristostatin

Abstract

Eristostatin, an RGD-containing disintegrin isolated from the venom of Eristicophis macmahoni, inhibits lung or liver colonization of melanoma cells in a mouse model. In this study, transwell migration and in vitro wound closure assays were used to determine the effect of eristostatin on the migration of melanoma cells. Eristostatin significantly impaired the migration of 5 human melanoma cell lines. Furthermore, it specifically inhibited cell migration on fibronectin in a concentration-dependent manner, but not on collagen IV or laminin. In contrast, eristostatin was found to have no effect on cell proliferation or angiogenesis. These results indicate that the interaction between eristostatin and melanoma cells may involve fibronectin-binding integrins that mediate cell migration. Mutation of 9 residues to alanine, seven within the RGD loop of eristostatin and two outside the RGD loop, resulted in significantly less potency in both platelet aggregation and wound closure assays. For seven of the mutations, however, decreased activity was found only in the latter assay. It is concluded that a different mechanism and/or integrin is involved in these two cell activities.