INTEGRIN-ALPHA(V)BETA(3) RESCUES MELANOMA-CELLS FROM APOPTOSIS IN 3-DIMENSIONAL DERMAL COLLAGEN

Human melanoma cells required ligation of the integrid (alpha(v) beta(3) to sustain viability and growth in three-dimensional dermal collagen. Variant melanoma cells, lacking the alpha(v) subunit, progressed rapidly to apoptosis within this matrix, whereas transfection of these cells with an alpha(v) cDNA restored (alpha(v) beta(3) expression and prevented apoptosis. Furthermore, inhibition of alpha(v) beta(3) ligation with a monoclonal antibody promoted cell death. Apoptosis of alpha(v)(-) cells within this matrix could be overcome by the addition of insulin or serum. However, alpha(v)(+) melanoma cells had a significant growth advantage in the presence of these growth factors. Initial adhesion of the melanoma cells to type I collagen depended on ligation of alpha(2) beta(1), but these cells can degrade this collagen to expose cryptic alpha(v) beta(3) binding sites. These findings provide evidence that the survival and growth of transformed cells may be regulated by collagen degradation and integrin-dependent anchorage to this proteolysed matrix.