Inhibition of melanoma cell motility by the snake venom disintegrin eristostatin.
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 five human melanoma cell lines. Furthermore, it specifically inhibited cell migration on fibronectin in a concentration-dependent manner, but not that 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. Mutations to alanine of seven residues within the RGD loop of eristostatin and four residues outside the RGD loop of eristostatin resulted in significantly less potency in both platelet aggregation and wound closure assays. For six of the mutations, however, decreased activity was found only in the latter assay. We conclude that a different mechanism and/or integrin is involved in these two cell activities.
Tian
Jing
J
Department of Medical Technology, University of Delaware, 305G Willard Hall, Education Building, Newark, DE 19716, USA.
Paquette-Straub
Carrie
C
Sage
E Helene
EH
Funk
Sarah E
SE
Patel
Vivek
V
Galileo
Deni
D
McLane
Mary Ann
MA
D000409:Alanine / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D049033:Chorioallantoic Membrane / Q000098:blood supply; D006801:Humans; D008545:Melanoma / Q000503:physiopathology; D051379:Mice; D016297:Mutagenesis, Site-Directed; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D011784:Quail / Q000196:embryology; D014757:Viper Venoms / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
D000970:Antineoplastic Agents; D010455:Peptides; D014757:Viper Venoms; C084060:eristostatin; D000409:Alanine