Caveolin-1 regulates glioblastoma aggressiveness through the control of α5β1 integrin expression and modulates glioblastoma responsiveness to SJ749, an α5β1 integrin antagonist
Caveolin-1 regulates glioblastoma aggressiveness through the control of α5β1 integrin expression and modulates glioblastoma responsiveness to SJ749, an α5β1 integrin antagonist
复制标题
DOI：
10.1016/j.bbamcr.2008.09.019
复制
发表时间：
2009-02-01
影响因子：
5.1
通讯作者：
Dontenwill, Monique
中科院分区：
文献类型：
--
作者：
Martin, Sophie;Cosset, Erika C.;Dontenwill, Monique
Caveolin-1在调节癌症中经常改变的过程中发挥检查点功能。虽然小窝蛋白-1的表达增加似乎是恶性胶质瘤家族中的常态，但在胶质母细胞瘤标本中，小窝蛋白-1阳性和阴性细胞群共存。由于迄今为止没有关于这些细胞对胶质母细胞瘤表型的贡献的数据，我们在胶质母细胞瘤细胞系U87 MG中操纵小窝蛋白-1。我们发现小窝蛋白-1在胶质母细胞瘤的侵袭性中起关键作用。我们确定整合素作为受小窝蛋白-1影响的主要基因。我们在这里报道了小窝蛋白-1调节后观察到的表型变化是由α（5）β（1）整合素介导的。作为小窝蛋白-1调节α（5）β（1）水平的结果，细胞对特异性α（5）β（1）整联蛋白拮抗剂SJ 749的敏感性受到影响。小窝蛋白-1效应的介导物α（5）β（1）整联蛋白也是胶质瘤侵袭性的标志物，并且是治疗胶质瘤特别是发挥最高侵袭性表型的胶质瘤的有效靶点。(c)2008 Elsevier B. V.保留所有权利。
Caveolin-1 plays a checkpoint function in the regulation of processes often altered in cancer. Although increased expression of caveolin-1 seems to be the norm in the glioma family of malignancies, populations of caveolin-1 positive and negative cells coexist among glioblastoma specimens. As no data are available to date on the contribution of such cells to the phenotype of glioblastoma, we manipulated caveolin-1 in the glioblastoma cell line U87MG. We showed that caveolin-1 plays a critical role in the aggressiveness of glioblastoma. We identified integrins as the main set of genes affected by caveolin-1. We reported here that the phenotypic changes observed after caveolin-1 modulation were mediated by alpha(5)beta(1) integrins. As a consequence of the regulation of alpha(5)beta(1) levels by caveolin-1, the sensitivity of cells to the specific alpha(5)beta(1) integrin antagonist, SJ749, was affected. Mediator of caveolin-1 effects, alpha(5)beta(1) integrin, is also a marker for glioma aggressiveness and an efficient target for the treatment of glioma especially the ones exerting the highest aggressive phenotype. (c) 2008 Elsevier B.V. All rights reserved.