Integrin alpha v beta 3 rescues melanoma cells from apoptosis in three-dimensional dermal collagen.
Human melanoma cells required ligation of the integrin 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.
Montgomery
A M
AM
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037.
Reisfeld
R A
RA
Cheresh
D A
DA
D017209:Apoptosis; D002448:Cell Adhesion; D003094:Collagen / Q000502:physiology*; D005782:Gels; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000502:physiology*; D008545:Melanoma / Q000473:pathology*; D016024:Receptors, Cytoadhesin / Q000502:physiology*; D019030:Receptors, Vitronectin; D012867:Skin; D014407:Tumor Cells, Cultured
D005782:Gels; D016023:Integrins; D016024:Receptors, Cytoadhesin; D019030:Receptors, Vitronectin; D003094:Collagen