Integrin α_vβ_3 Rescues Melanoma Cells from Apoptosis in Three-Dimensional Dermal Collagen
Abstract
Human melanoma cells required ligation of the integrin α_vβ_3 to sustain viability and growth in three-dimensional dermal collagen. Variant melanoma cells, lacking the α_v subunit, progressed rapidly to apoptosis within this matrix, whereas transfection of these cells with an α_v cDNA restored α_vβ_3 expression and prevented apoptosis. Furthermore, inhibition of α_vβ_3 ligation with a monoclonal antibody promoted cell death. Apoptosis of α_v(-) cells within this matrix could be overcome by the addition of insulin or serum. However, α_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 α_2β_1, but these cells can degrade this collagen to expose cryptic α_vβ_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.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- September 1994
- DOI:
- 10.1073/pnas.91.19.8856
- Bibcode:
- 1994PNAS...91.8856M