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Suppression of tumor angiogenesis through the inhibition of integrin function and signaling in endothelial cells: which side to target?

Authors :
Rüegg C
Dormond O
Foletti A
Source :
Endothelium : journal of endothelial cell research [Endothelium] 2002; Vol. 9 (3), pp. 151-60.
Publication Year :
2002

Abstract

Tumor angiogenesis is an essential step in tumor progression and metastasis formation. Suppression of tumor angiogenesis results in the inhibition of tumor growth. Recent evidence indicates that vascular integrins, in particular alpha V beta 3, are important regulators of angiogenesis, including tumor angiogenesis. Integrin alpha V beta 3 antagonists, such as blocking antibodies or peptides, suppress tumor angiogenesis and tumor progression in many preclinical tumor models. The potential therapeutic efficacy of extracellular integrin antagonists in human cancer is currently being tested in clinical trials. Selective disruption of the tumor vasculature by high doses of tumor necrosis factor (TNF) and interferon gamma (IFN-gamma), and the antiangiogenic activity of nonsteroidal anti-inflammatory drugs are associated with the suppression of integrin alpha V beta 3 function and signaling in endothelial cells. Furthermore, expression of isolated integrin cytoplasmic domains disrupts integrin-dependent adhesion, resulting in endothelial cell detachment and apoptosis. These results confirm the critical role of vascular integrins in promoting endothelial cell survival and angiogenesis and suggest that intracellular targeting of integrin function and signaling may be an alternative strategy to extracellular integrin antagonists for the therapeutic inhibition of tumor angiogenesis.

Details

Language :
English
ISSN :
1062-3329
Volume :
9
Issue :
3
Database :
MEDLINE
Journal :
Endothelium : journal of endothelial cell research
Publication Type :
Academic Journal
Accession number :
12380640
Full Text :
https://doi.org/10.1080/10623320213635