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Integrin alpha(v)beta(3)-mediated activation of apoptosis
D L Brassard1, E Maxwell, M Malkowski
1Department of Tumor Biology, Schering-Plough Research Institute, K-15-4-4600, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA.
Experimental Cell Research
|August 10, 1999
Summary
Alpha(v)beta(3) integrin antagonists induce apoptosis before cell detachment, unlike anoikis. This suggests distinct signaling pathways with implications for alpha(v)beta(3) integrin antagonists as anti-tumor agents.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Alpha(v)beta(3) integrin is crucial for endothelial and tumor cell survival through extracellular matrix interactions.
- The survival signaling of alpha(v)beta(3) integrin is adhesion-dependent, but direct comparisons with antagonist effects are lacking.
Purpose of the Study:
- To investigate the differential cellular responses to alpha(v)beta(3) integrin antagonist treatment versus suspension-induced anoikis.
- To determine if alpha(v)beta(3) integrin expression confers differential survival pathways in epithelial cells.
Main Methods:
- Transfected human embryonic kidney 293 cells with alpha(v)beta(3) integrin.
- Treated cells with the alpha(v)beta(3) antagonist echistatin.
- Cultured cells in suspension and compared apoptotic responses.
Main Results:
- Alpha(v)beta(3) integrin expression transferred survival pathways to epithelial cells.
- Echistatin treatment induced apoptosis preceding cell detachment.
- Apoptosis induced by echistatin differed in kinetics from anoikis in suspended cells.
Conclusions:
- Alpha(v)beta(3) integrin antagonist-induced apoptosis has distinct kinetics compared to anoikis.
- Aberrant alpha(v)beta(3) integrin expression in tumors may be targeted by antagonists.
- These findings support the potential of alpha(v)beta(3) integrin antagonists as anti-tumor therapies.