期刊
CANCER RESEARCH
卷 66, 期 12, 页码 6002-6007出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-05-4105
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The potential role of alpha(5)beta(1) integrins in cancer has recently attracted much interest. However, few alpha(5)beta(1)-selective antagonists have been developed compared with other integrins. The most specific nonpeptidic alpha(5)beta(1) 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 alpha(5)beta(1). 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 G(0)-G(1) 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 alpha(5)beta(1) than A172 cells, we specifically examined the effect of SJ749 on A172 cells overexpressing alpha(5). Treatment of alpha(5)beta(1) 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 alpha(5)beta(1) expression. Our study highlights the importance of alpha(5)beta(1) as an anticancer target and shows for the first time that a small nonpeptidic alpha(5)beta(1)-specific antagonist affects proliferation of tumor cells.
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