Serine protease inhibitor (SERPIN) B1 suppresses cell migration and invasion in glioma cells
Serine protease inhibitor (SERPIN) B1 suppresses cell migration and invasion in glioma cells
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DOI：
10.1016/j.brainres.2014.06.017
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发表时间：
2015-03-10
期刊：
影响因子：
2.9
通讯作者：
Zhu, Jianhong
中科院分区：
文献类型：
--
作者：
Gao, Huasong;Ding, Zongmei;Zhu, Jianhong
丝氨酸蛋白酶抑制因子(SERPIN)B1在许多人类肿瘤中都有表达，但对其在胶质瘤病理生理学中的作用知之甚少。在本文中，我们报道了serpinB1在高级别人脑胶质瘤组织样本和胶质母细胞瘤细胞系中的表达下调。为了研究serpinB1在胶质瘤迁移和侵袭中的作用，我们建立了serpinB1过表达或缺失的人脑胶质瘤细胞系。SerpinB1的过表达抑制了胶质瘤细胞的迁移和侵袭，而serpinB1的去除则促进了胶质瘤细胞的迁移和侵袭。SerpinB1可能通过抑制基质金属蛋白酶-2(MMP2)的表达而抑制胶质瘤的迁移和侵袭。分子数据显示，serpinB1在胶质瘤细胞中的作用可能是通过持续失活参与下调MMP-2表达的粘着斑激酶(FAK)的磷酸化来实现的。多因素分析显示，在胶质瘤中，serpinB1的高表达与良好的预后相关。综上所述，我们的研究结果表明，serpinB1可能通过抑制基质金属蛋白酶-2的表达和FAK的激活来负向调节胶质瘤细胞的迁移和侵袭。我们认为，serpinB1可能在临床医学上有应用价值。(C)2014爱思唯尔B.V.保留所有权利。
The serine protease inhibitor (SERPIN) B1 is expressed in numerous human tumors, but little is known regarding its role in the pathophysiology of glioma. In this paper, we report that SERPINB1 expression was down-regulated in high-grade human glioma tissue samples and glioblastoma cell lines. To investigate the role of SERPINB1 in glioma migration and invasion, we generated human glioma cell lines in which SERPINB1 was either overexpressed or depleted. Overexpression of SERPINB1 suppressed, while elimination of SERPINB1 promoted, the migration and invasion of glioma cells. SERPINB1 inhibited glioma migration and invasion probably by dampening the expression of matrix metalloproteinase-2 (MMP-2). Molecular data showed that the effect of SERPINB1 in glioma cells might be mediated via sustained inactivation of the phosphorylation of focal adhesion kinase (FAK) involved in the downregulation of the expressions of MMP-2. In a multivariate analysis, high SERPINB1 expression was showed to be associated with good prognosis in glioma. In conclusion, our data suggest that SERPINB1 negatively regulates glioma cell migration and invasion probably by abrogating the expression of MMP-2 and the activation of FAK. We suggest that SERPINB1 may offer the application in clinical medicine. (C) 2014 Elsevier B.V. All rights reserved.