Department of Radiation Oncology, School of Medicine, Vanderbilt University, Nashville, TN 37232, USA.
Cancer Lett. 2013 Jan 1;328(1):55-64. doi: 10.1016/j.canlet.2012.09.011. Epub 2012 Sep 23.
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.
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。
