Cadherin-11, a Marker of the Mesenchymal Phenotype, Regulates Glioblastoma Cell Migration and Survival In Vivo
Cadherin-11, a Marker of the Mesenchymal Phenotype, Regulates Glioblastoma Cell Migration and Survival In Vivo
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DOI：
10.1158/1541-7786.mcr-11-0457
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发表时间：
2012-03-01
影响因子：
5.2
通讯作者：
Brady-Kalnay, Susann M.
中科院分区：
文献类型：
--
作者：
Kaur, Harpreet;Phillips-Mason, Polly J.;Brady-Kalnay, Susann M.
多形性胶质母细胞瘤（GBM）是星形细胞瘤中最恶性和最致命的形式。GBM患者的生存时间约为1年，需要鉴定新的分子靶点和更有效的治疗方法。钙粘蛋白-11是一种钙依赖性细胞间粘附分子和间充质标志物，在正常组织发育和癌细胞迁移中起作用。钙粘蛋白-11在GBM中的功能意义尚未研究。在这里，我们表明，钙粘蛋白-11表达在人类GBM肿瘤和人类胶质瘤干细胞样细胞的免疫组织化学标记。此外，我们表明，钙粘蛋白-11在人脑胶质瘤细胞系中表达的免疫印迹。短发夹RNA介导的人胶质瘤细胞系中钙粘蛋白-11表达的敲低导致体外迁移和生长因子非依赖性细胞存活减少更重要的是，钙粘蛋白-11的敲低抑制了异位和原位小鼠异种移植模型中的胶质瘤细胞存活。总之，我们的研究结果显示了钙粘蛋白-11在GBM中表达的功能意义，并为钙粘蛋白-11在体内环境中促进胶质瘤细胞存活的新作用提供了证据。因此，我们的研究表明钙粘蛋白-11是一个可行的分子靶点，用于GBM的治疗干预。Mol Cancer Res; 10（3）; 293-304.（C）2012年AACR。
Glioblastoma multiforme (GBM) is the most malignant and lethal form of astrocytoma. The GBM patient survival time of approximately 1 year necessitates the identification of novel molecular targets and more effective therapeutics. Cadherin-11, a calcium-dependent cell-cell adhesion molecule and mesenchymal marker, plays a role in both normal tissue development and in cancer cell migration. The functional significance of cadherin-11 in GBM has not been investigated. Here, we show that cadherin-11 is expressed in human GBM tumors and human glioma stem-like cells by immunohistochemical labeling. In addition, we show that cadherin-11 is expressed in human glioma cell lines by immunoblotting. Short hairpin RNA-mediated knockdown of cadherin-11 expression in human glioma cell lines results in decreased migration and growth factor-independent cell survival in vitro. More importantly, knockdown of cadherin-11 inhibits glioma cell survival in heterotopic and orthotopic mouse xenograft models. Together, our results show the functional significance of cadherin-11 expression in GBM and provide evidence for a novel role of cadherin-11 in promoting glioma cell survival in an in vivo environment. Thus, our studies suggest cadherin-11 is a viable molecular target for therapeutic intervention in GBM. Mol Cancer Res; 10(3); 293-304. (C)2012 AACR.