
<ArticleTitle>NSAIDs inhibit <prot>alpha V beta 3 integrin</prot>-mediated and <prot>Cdc42</prot>/<prot>Rac</prot>-dependent endothelial-cell spreading, migration and angiogenesis.</ArticleTitle>
<AbstractText><prot>Cyclooxygenase-2</prot> (<prot>COX-2</prot>), a key enzyme in arachidonic acid metabolism, is overexpressed in many cancers. Inhibition of <prot>COX-2</prot> 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. <prot>Integrin alpha V beta 3</prot> is an adhesion receptor critically involved in mediating tumor angiogenesis. Here we show that inhibition of endothelial-cell <prot>COX-2</prot> by NSAIDs suppresses alpha V beta 3-dependent activation of the small GTPases <prot>Cdc42</prot> and <prot>Rac</prot>, resulting in inhibition of endothelial-cell spreading and migration in vitro and suppression of <prot>fibroblast growth factor-2</prot>-induced angiogenesis in vivo. These results establish a novel functional link between <prot>COX-2</prot>, <prot>integrin alpha V beta 3</prot> and <prot>Cdc42</prot>-/<prot>Rac</prot>-dependent endothelial-cell migration. Moreover, they provide a rationale to the understanding of the anti-angiogenic activity of NSAIDs.</AbstractText>
