Human melanoma cells expressing the αvβ3 integrin are partially protected from necrotic cell death induced by dynamic matrix detachment

Anchorage-independence is a hallmark of metastatic cancer cells. In previous studies we characterized a novel model for anchorage-independence employing dynamic matrix detachment (DMD) using rotation in low shear stress conditions. We observed that in contrast to the classical apoptosis-inducing static matrix detachment (SMD) model, the venous circulation-mimicking DMD model induced necrosis in transformed cells. In the current study we revisited the mechanism of DMD-induced cell death and evaluated the contribution of alpha v beta 3 integrin overexpression in human melanoma cells to anchorage-independence in DMD. DMD cell culture induced primarily necrosis in the melanoma cells studied. alpha v beta 3, but not the control related alpha IIb beta 3 integrin, could confer survival advantage in DMD. While apoptosis was unaffected, constitutive, unligated alpha v beta 3 overexpression was associated with attenuation of necrosis in DMD. alpha v beta 3 overexpressing melanoma cells manifested AKT activation that was independent of DMD conditions. Furthermore, while a small molecular inhibitor of Ala phosphorylation induced apoptosis in adherent cells, in DMD conditions it had no effect on cell outcome. Thus, alpha v beta 3-overexpressing melanoma cells are partially protected from DMD-induced cell death in an apoptosis-independent mechanism. This finding may be one of the factors accounting for anchorage-independence in circulating metastatic melanoma cells. (C) 2009 Elsevier Ireland Ltd. All rights reserved.