Integrin αvβ3Rescues Melanoma Cells from Apoptosis in Three-Dimensional Dermal Collagen

Human melanoma cells required ligation of the integrin αvβ3to sustain viability and growth in three-dimensional dermal collagen. Variant melanoma cells, lacking the αvsubunit, progressed rapidly to apoptosis within this matrix, whereas transfection of these cells with an αvcDNA restored αvβ3expressi...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1994-09, Vol.91 (19), p.8856-8860
Main Authors: Anthony M. P. Montgomery, Reisfeld, Ralph A., Cheresh, David A.
Format: Article
Language:English
Subjects:
Apoptosis
Cell adhesion
Cell growth
Cell nucleus
Cells
Collagens
Gels
Integrins
Ligation
Melanoma
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Summary:Human melanoma cells required ligation of the integrin αvβ3to sustain viability and growth in three-dimensional dermal collagen. Variant melanoma cells, lacking the αvsubunit, progressed rapidly to apoptosis within this matrix, whereas transfection of these cells with an αvcDNA restored αvβ3expression and prevented apoptosis. Furthermore, inhibition of αvβ3ligation with a monoclonal antibody promoted cell death. Apoptosis of αv(-) cells within this matrix could be overcome by the addition of insulin or serum. However, αv(+) 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 α2β1, but these cells can degrade this collagen to expose cryptic αvβ3binding 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.
ISSN:0027-8424
DOI:10.1073/pnas.91.19.8856