Endothelial cell integrins and COX-2: mediators and therapeutic targets of tumor angiogenesis.

Détails

ID Serval
serval:BIB_191CCD9DD452
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Synthèse (review): revue aussi complète que possible des connaissances sur un sujet, rédigée à partir de l'analyse exhaustive des travaux publiés.
Collection
Publications
Institution
Titre
Endothelial cell integrins and COX-2: mediators and therapeutic targets of tumor angiogenesis.
Périodique
Biophysica Acta-Reviews on Cancer
Auteur⸱e⸱s
Rüegg C., Dormond O., Mariotti A.
ISSN
0304-419X
ISSN-L
1879-2561
Statut éditorial
Publié
Date de publication
2004
Peer-reviewed
Oui
Volume
1654
Numéro
1
Pages
51-67
Langue
anglais
Résumé
Vascular integrins are essential regulators and mediators of physiological and pathological angiogenesis, including tumor angiogenesis. Integrins provide the physical interaction with the extracellular matrix (ECM) necessary for cell adhesion, migration and positioning, and induce signaling events essential for cell survival, proliferation and differentiation. Integrins preferentially expressed on neovascular endothelial cells, such as alphaVbeta3 and alpha5beta1, are considered as relevant targets for anti-angiogenic therapies. Anti-integrin antibodies and small molecular integrin inhibitors suppress angiogenesis and tumor progression in many animal models, and are currently tested in clinical trials as anti-angiogenic agents. Cyclooxygense-2 (COX-2), a key enzyme in the synthesis of prostaglandins and thromboxans, is highly up-regulated in tumor cells, stromal cells and angiogenic endothelial cells during tumor progression. Recent experiments have demonstrated that COX-2 promotes tumor angiogenesis. Chronic intake of nonsteroidal anti-inflammatory drugs and COX-2 inhibitors significantly reduces the risk of cancer development, and this effect may be due, at least in part, to the inhibition of tumor angiogenesis. Endothelial cell COX-2 promotes integrin alphaVbeta3-mediated endothelial cell adhesion, spreading, migration and angiogenesis through the prostaglandin-cAMP-PKA-dependent activation of the small GTPase Rac. In this article, we review the role of integrins and COX-2 in angiogenesis, their cross talk, and discuss implications relevant to their targeting to suppress tumor angiogenesis.
Mots-clé
Angiogenesis Inhibitors/therapeutic use, Animals, Cell Adhesion, Cell Movement, Cell Survival, Cyclooxygenase 2, Drug Delivery Systems, Endothelial Cells/drug effects, Endothelial Cells/metabolism, Humans, Integrin alphaVbeta3/metabolism, Integrins/antagonists & inhibitors, Integrins/chemistry, Isoenzymes/antagonists & inhibitors, Isoenzymes/chemistry, Ligands, Membrane Proteins, Neoplasms/blood supply, Neoplasms/drug therapy, Neovascularization, Pathologic/drug therapy, Neovascularization, Pathologic/etiology, Prostaglandin-Endoperoxide Synthases/chemistry, Prostaglandin-Endoperoxide Synthases/metabolism, Signal Transduction
Pubmed
Web of science
Création de la notice
28/01/2008 8:34
Dernière modification de la notice
20/08/2019 12:49
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