ASSESSMENT OF THE IN VITRO ACTIVITY OF RGDECHI-HCIT, alpha V beta3 INTEGRIN ANTAGONIST, ON MALIGNANT MELANOMA CELLS

In malignant melanoma (MM), one of the most aggressive cancers, changes in integrin expression and intracellular control of integrin function are involved in the conversion from a stationary to a migratory and invasive phenotype, key step toward the progression of this tumor. Overexpression of alphav beta 3 integrin is linked to a more metastatic phenotype. Therefore, development of anti-?alphav beta 3 agents able to counteract the progression of melanoma would be helpful for the disease treatment. A new highly selective ligand of alphav beta 3, referred to as RGDechi-hCit, containing a cyclic RGD motif with two echistatin moieties, has been demonstrated to have anti-angiogenic properties against endothelial cells in animal models of angiogenesis. Aim of this study was to evaluate the in vitro effects of the RGDechi-hCit peptide on MM cell lines. C Cytofluorimetric analysis allowed the characterization of cell surface expression of alphav beta 3 integrin on seven MM cell lines. Cell proliferation, adhesion, and migration assays were carried out on these MM cells in the presence of the?alphav beta 3-antagonist RGDechi-hCit. Proliferation was not significantly inhibited by RGDechi-hCit but, striking morphological changes were detected in MM cell lines highly expressing alphav beta 3, suggesting a specific role of this integrin in adhesion and migration. Assays on fibronectin-coated plates showed indeed a significant RGDechi-hCit dose-dependent inhibitory effect on both adhesion (p = 0.024) and migration (p < 0.001).Our data demonstrate anti-adhesion and anti-migration, but not anti-proliferative, activities of RGDechi-hCit against MM cells.