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Suppression of tumor angiogenesis through the inhibition of integrin function and signaling in endothelial cells: which side to target?
- 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.
- Subjects :
- Angiogenesis Inhibitors pharmacology
Cell Adhesion Molecules physiology
Cyclooxygenase 2
Drug Delivery Systems
Endothelium, Vascular cytology
Endothelium, Vascular metabolism
Humans
Integrin alphaVbeta3 antagonists & inhibitors
Interferon-gamma pharmacology
Isoenzymes pharmacology
Membrane Proteins
Neoplasms drug therapy
Neoplasms metabolism
Neovascularization, Pathologic
Prostaglandin-Endoperoxide Synthases pharmacology
Signal Transduction drug effects
Tumor Necrosis Factor-alpha pharmacology
rho GTP-Binding Proteins metabolism
Angiogenesis Inhibitors therapeutic use
Endothelium, Vascular drug effects
Integrins antagonists & inhibitors
Neoplasms blood supply
Subjects
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