Abstract：
:The potential role of alpha5beta1 integrins in cancer has recently attracted much interest. However, few alpha5beta1-selective antagonists have been developed compared with other integrins. The most specific nonpeptidic alpha5beta1 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 alpha5beta1. 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 alpha5beta1 than A172 cells, we specifically examined the effect of SJ749 on A172 cells overexpressing alpha5. Treatment of alpha5-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 alpha5beta1 expression. Our study highlights the importance of alpha5beta1 as an anticancer target and shows for the first time that a small nonpeptidic alpha5beta1-specific antagonist affects proliferation of tumor cells.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Maglott A,Bartik P,Cosgun S,Klotz P,Rondé P,Fuhrmann G,Takeda K,Martin S,Dontenwill Mdoi
10.1158/0008-5472.CAN-05-4105subject
Has Abstractpub_date
2006-06-15 00:00:00pages
6002-7issue
12eissn
0008-5472issn
1538-7445pii
66/12/6002journal_volume
66pub_type
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