Effect of VP12 and viperistatin on inhibition of collagen receptors: dependent melanoma metastasis

Abstract

Viperistatin and VP12 isolated from Vipera paleastinae venom showed a potent inhibitory

activity against collagen receptors, α1β1 and α2β1 integrins, respectively. Structurally,

viperistatin belongs to the disintegrin family of proteins, whereas VP12 is composed of two

subunits VP12A and VP12B displaying amino acid sequence homology with heterodimeric C-

lectin type proteins. Viperistatin and VP12 used separately and simultaneously inhibited pro-

metastatic activities of melanoma cells lines. The level of inhibition of MV3 and HS.939T

human cell lines in cell adhesion and migration assays by both compounds was correlated with

expression of α1β1 and α2β1 integrins on the cell surface. MV3 cells express collagen receptors

to much higher extent than HS.939T and required the application of higher concentrations of

inhibitors to block their adhesion to collagen types I and IV. A melanoma cell transmigration

assay through a dHMVEC layer revealed that α1β1 integrin plays a significant role in invasion

of HS.939T cells, while α2β1 integrin appears to be more important for MV3 cells. In an animal

model of hematogenous metastasis of the mouse B16F10 cell line, the inhibitory effect of

viperistatin and VP12 was only partial. These data suggest that collagen receptors may be an

interesting target for development of new anti-metastatic therapies.