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 collage n. Variant melanoma cells, lacking the alpha(v) subunit, progressed ra pidly to apoptosis within this matrix, whereas transfection of these c ells with an alpha(v) cDNA restored (alpha(v) beta(3) expression and p revented apoptosis. Furthermore, inhibition of alpha(v) beta(3) ligati on with a monoclonal antibody promoted cell death. Apoptosis of alpha( v)(-) cells within this matrix could be overcome by the addition of in sulin or serum. However, alpha(v)(+) melanoma cells had a significant growth advantage in the presence of these growth factors. Initial adhe sion 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 evidenc e that the survival and growth of transformed cells may be regulated b y collagen degradation and integrin-dependent anchorage to this proteo lysed matrix.