Integrin alpha(V)beta(3) promotes M21 melanoma growth in human skin by regulating tumor cell survival

Growth and dissemination of malignant melanoma has a profound impact on our population, and little is known concerning the mechanisms controlling this disease in humans. Evidence is provided that integrin alpha(v)beta(3) play s a critical role in M21 melanoma tumor survival within human skin by a mec hanism independent of its known role in angiogenesis, Antagonists of alpha( v)beta(3) blocked melanoma growth by inducing tumor apoptosis, Moreover, M2 1 melanoma cell interactions with denatured collagen, a known ligand for al pha(v)beta(3), caused a 5-fold increase in the relative Bcl-2:Bax ratio, an event thought to promote cell survival, Importantly, denatured collagen co localized with alpha(v)beta(3)-expressing melanoma cells in human tumor bio psies, suggesting that alpha(v)beta(3) interaction with denatured collagen may play a critical role in melanoma tumor survival in vivo.