αV integrin promotes in vitro and in vivo survival of cells in metastatic melanoma

摘要: The expression of integrin αV subunit on 4 melanoma-derived cell lines (A2058, SK-mel-5, WM-115 and WM-266-4) was analyzed. cells, which originate from a primary tumor, were negative, whereas all 3 metastasis-derived had high levels αV. To study integrins in the survival melanoma we developed novel strategy that is exempt extracellular inhibitors ligand binding, can activate signaling have integrin-independent effects apoptosis. A recombinant adenovirus used to transfer cDNA coding for single-chain intracellular anti-αV antibody into cells. Anti-αV effectively inhibited surface integrins. In culture experiments, depletion detached cells matrix induced Moreover, it prevented WM-266-4 forming tumors severe combined immunodeficiency mice but could not prevent growth formed by αV-negative Our results indicate melanomas there are survive without integrins, during progression disease develop dependency these receptors. Furthermore, data oppose possibility apoptosis occur due direct activation caspases ligand-free surface. © 2004 Wiley-Liss, Inc.