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Tax-interacting protein 1(TIP-1)的表达促进了人胶质母细胞瘤细胞在裸鼠中的血管生成和肿瘤形成。

Expression of Tax-interacting protein 1 (TIP-1) facilitates angiogenesis and tumor formation of human glioblastoma cells in nude mice.

机构信息

Department of Radiation Oncology, School of Medicine, Vanderbilt University, Nashville, TN 37232, USA.

出版信息

Cancer Lett. 2013 Jan 1;328(1):55-64. doi: 10.1016/j.canlet.2012.09.011. Epub 2012 Sep 23.

Abstract

Glioblastoma is the most common and fatal type of primary brain tumors featured with hyperplastic blood vessels. Here, we performed meta-analyses of published data and established a correlation between high TIP-1 expression levels and the poor prognosis of glioblastoma patients. Next, we explored the biological relevance of TIP-1 expression in the pathogenesis of glioblastoma. By using orthotopic and heterotopic mouse models of human glioblastomas, this study has characterized TIP-1 as one contributing factor to the tumor-driven angiogenesis. In vitro and in vivo functional assays, along with biochemical analyses with microarrays and antibody arrays, have demonstrated that TIP-1 utilizes multiple pathways including modulating fibronectin gene expression and uPA protein secretion, to establish or maintain a pro-angiogenic microenvironment within human glioblastoma. In conclusion, this work supports one hypothesis that TIP-1 represents a novel prognostic biomarker and a therapeutic target of human glioblastoma.

摘要

胶质母细胞瘤是最常见和致命的原发性脑肿瘤,其特征为血管过度增生。在这里,我们对已发表的数据进行了荟萃分析,并建立了 TIP-1 高表达水平与胶质母细胞瘤患者预后不良之间的相关性。接下来,我们探讨了 TIP-1 表达在胶质母细胞瘤发病机制中的生物学相关性。通过使用人类胶质母细胞瘤的原位和异位小鼠模型,本研究将 TIP-1 特征化为肿瘤驱动血管生成的一个促成因素。体外和体内功能测定,以及微阵列和抗体阵列的生化分析,表明 TIP-1 利用多种途径,包括调节纤维连接蛋白基因表达和 uPA 蛋白分泌,在人胶质母细胞瘤内建立或维持促血管生成的微环境。总之,这项工作支持了一个假设,即 TIP-1 代表了一种新的胶质母细胞瘤预后标志物和治疗靶点。

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