Abstract

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 thistumor. 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.

Autore Pugliese

• Saviano Michele

Tutti gli autori

• M. Pisano; V. Nieddu; L. Zaccaro; I. Sassu; S. Cossu; A. Del Gatto; I. De Paola; G. Galleri; M. Saviano; G. Palmieri; C. Rozzo.

Titolo volume/Rivista

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Anno di pubblicazione

2012

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Settori ERC

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