NSAIDs inhibit alpha V beta 3 integrin-mediated and Cdc42/Rac-dependent endothelial-cell spreading, migration and angiogenesis.

Détails

ID Serval
serval:BIB_8F5675D259C1
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
NSAIDs inhibit alpha V beta 3 integrin-mediated and Cdc42/Rac-dependent endothelial-cell spreading, migration and angiogenesis.
Périodique
Nature Medicine
Auteur(s)
Dormond O., Foletti A., Paroz C., Rüegg C.
ISSN
1078-8956 (Print)
ISSN-L
1078-8956
Statut éditorial
Publié
Date de publication
2001
Volume
7
Numéro
9
Pages
1041-1047
Langue
anglais
Résumé
Cyclooxygenase-2 (COX-2), a key enzyme in arachidonic acid metabolism, is overexpressed in many cancers. Inhibition of COX-2 by nonsteroidal anti-inflammatory drugs (NSAIDs) reduces the risk of cancer development in humans and suppresses tumor growth in animal models. The anti-cancer effect of NSAIDs seems to involve suppression of tumor angiogenesis, but the underlying mechanism is not completely understood. Integrin alpha V beta 3 is an adhesion receptor critically involved in mediating tumor angiogenesis. Here we show that inhibition of endothelial-cell COX-2 by NSAIDs suppresses alpha V beta 3-dependent activation of the small GTPases Cdc42 and Rac, resulting in inhibition of endothelial-cell spreading and migration in vitro and suppression of fibroblast growth factor-2-induced angiogenesis in vivo. These results establish a novel functional link between COX-2, integrin alpha V beta 3 and Cdc42-/Rac-dependent endothelial-cell migration. Moreover, they provide a rationale to the understanding of the anti-angiogenic activity of NSAIDs.
Mots-clé
Animals, Anti-Inflammatory Agents, Non-Steroidal/pharmacology, Cell Division/drug effects, Cell Movement/drug effects, Cells, Cultured, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Cyclooxygenase Inhibitors/pharmacology, Dinoprostone/pharmacology, Endothelium, Vascular/cytology, Endothelium, Vascular/drug effects, Fibroblast Growth Factor 2/pharmacology, Humans, Isoenzymes/antagonists & inhibitors, Membrane Proteins, Mice, Mice, Nude, Neovascularization, Physiologic/drug effects, Nitrobenzenes/pharmacology, Prostaglandin-Endoperoxide Synthases, Receptors, Vitronectin/antagonists & inhibitors, Receptors, Vitronectin/metabolism, Sulfonamides/pharmacology, Thromboxane A2/pharmacology, cdc42 GTP-Binding Protein/drug effects, cdc42 GTP-Binding Protein/metabolism, rac GTP-Binding Proteins/drug effects, rac GTP-Binding Proteins/metabolism
Pubmed
Web of science
Création de la notice
28/01/2008 9:36
Dernière modification de la notice
03/03/2018 19:21
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