期刊
CANCER LETTERS
卷 328, 期 1, 页码 55-64出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2012.09.011
关键词
TIP-1; PDZ; Glioblastoma; Angiogenesis; Fibronectin; uPA
类别
资金
- NIH [R01CA127482, P50 CA128323]
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. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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