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

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

  • 2001-09-05
Published in:
  • Nature medicine. - 2001
Animals
Anti-Inflammatory Agents, Non-Steroidal
Cell Division
Cell Movement
Cells, Cultured
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Dinoprostone
Endothelium, Vascular
Fibroblast Growth Factor 2
Humans
Isoenzymes
Membrane Proteins
Mice
Mice, Nude
Neovascularization, Physiologic
Nitrobenzenes
Prostaglandin-Endoperoxide Synthases
Receptors, Vitronectin
Sulfonamides
Thromboxane A2
cdc42 GTP-Binding Protein
rac GTP-Binding Proteins
English 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.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/277867
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