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• W2036998931 abstract "Abstract The potential role of α5β1 integrins in cancer has recently attracted much interest. However, few α5β1-selective antagonists have been developed compared with other integrins. The most specific nonpeptidic α5β1 antagonist described thus far, SJ749, inhibits angiogenesis by affecting adhesion and migration of endothelial cells. We investigated the effects of SJ749 in two human astrocytoma cell lines, A172 and U87, which express different levels of α5β1. SJ749 dose-dependently inhibited adhesion of both cell types on fibronectin. Application of SJ749 to spread cells led to formation of nonadherent spheroids for A172 cells but had no effect on U87 cell morphology. SJ749 also reduced proliferation of A172 cells due to a long lasting G0-G1 arrest, whereas U87 cells were only slightly affected. However, under nonadherent culture conditions (soft agar), SJ749 significantly reduced the number of colonies formed only by U87 cells. As U87 cells express more α5β1 than A172 cells, we specifically examined the effect of SJ749 on A172 cells overexpressing α5. Treatment of α5-A172 cells with SJ749 decreased colony formation similarly to that observed in U87 cells. Therefore, in nonadherent conditions, the effect of SJ749 on tumor cell growth characteristics depends on the level of α5β1 expression. Our study highlights the importance of α5β1 as an anticancer target and shows for the first time that a small nonpeptidic α5β1-specific antagonist affects proliferation of tumor cells. (Cancer Res 2006; 66(12): 6002-7)" @default.
• W2036998931 created "2016-06-24" @default.
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• W2036998931 date "2006-06-15" @default.
• W2036998931 modified "2023-10-15" @default.
• W2036998931 title "The Small α5β1 Integrin Antagonist, SJ749, Reduces Proliferation and Clonogenicity of Human Astrocytoma Cells" @default.
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• W2036998931 doi "https://doi.org/10.1158/0008-5472.can-05-4105" @default.
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