Year: 2014
Type: editorial
Abstract: We and others have demonstrated that antagonists of αv integrins target and suppress pathological angiogenesis, resulting in decreased tumor growth, 9,10 inflammatory disease, 9,11 and retinal disease. 5In glioblastoma patients treated with these agents, some clinical efficacy was noted, 12 although overall survival was not significantly impacted in recently announced phase III trials.Studies by Hynes et al showed that mice deficient in either αv or β3 showed robust blood vessel development. 13,14In fact, these animals displayed enhanced endothelial cell VEGF receptor (VEGFR) expression associated with increased tumor angiogenesis.This led the authors to conclude that αvβ3 plays a negative role in angiogenesis.How, then, can one reconcile the fact that αvβ3 antagonists suppress angiogenesis in mice and humans?In an elegant series of studies, Steri et al 7 examined the effects of acute depletion of endothelial cell integrin αvβ3 on neovascularization via Cre-mediated inactivation of a floxed β3 gene.Complementary approaches were used in this multicenter tour de force of mouse genetics, including Tie2-driven expression of Cre and hydroxytamoxifen-inducible expression of Cre driven by platelet-derived growth factor b promoters.The finding by Steri et al 7 that αvβ3 is required for angiogenesis is consistent with previous studies by Byzoya and et al,15 Tumor Angiogenesis Putting a Value on Plastic GEMMs
Source: Circulation Research
Authors: David A. Cheresh, Dwayne G. Stupack
Institutions: University of California San Diego, Moores Cancer Center
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2007717639