脑血管内皮细胞介导神经胶质母细胞瘤沿血管侵袭的机制研究

As one of the most common primary brain tumor, Glioblastoma multiforme （GBM） earning a poor prognosis in clinical therapy mainly caused by its diffused growth nature, the median overall survival rate of GBM patients was about 12.1-14.6 months. Unfortunately, the mechanism of glioblastoma invasion was still unclear. In our previous study, we found GBM tumor cells display a tendency to co-opt host blood vessels during invasion, and those invading cells presenting EMT characters. Brain microvascular endothelial cells (BMECs) have been demonstrated owning the potency to recruit Glioblastoma stem cells (GSCs) and induce the EMT of glioblastoma cells by secreting TGF-βand SDF-1. These finds suggest a mechanism of glioblastoma invasion: GSCs were gained the ability of invasion through EMT and recruited to endothelial cells via the SDF-1/CXCR4 axis, and then glioblastoma cells spread all over the brain by coopting and migrating along the cerebral vascular scaffold . This project focuses on the interaction between BMECs and GBM cells during GBM invasion to study the molecular mechanism in GBM cell EMT and vessel co-option on clinical sample, time-lapse zebrafish xenograft model and in vitro 3D cell culture .

胶质母细胞瘤（GBM）是常见的恶性颅内肿瘤，目前病人的中位生存期为12.1-14.6个月。胶质母细胞瘤病人预后差的根本原因在于肿瘤在脑部的恶性侵袭（Invasion），但是其机制还不明确。在前期工作中我们发现GBM肿瘤细胞通常沿血管侵袭（Vessel co-option），并呈现出上皮间充质转化（EMT）的特征。近期研究同时表明脑血管内皮细胞能分泌TGF-β，SDF-1等相关因子，提示脑血管内皮细胞可能介导了胶质母细胞瘤侵袭。于是我们猜测GBM肿瘤侵袭的可能机制：在脑血管内皮细胞诱导和招募下GBM肿瘤细胞干细胞（GSCs）通过上皮间充质转化（EMT）获得侵袭能力并不断靠近血管，最后沿血管支架向外侵袭。本项目旨在采用临床标本检测、斑马鱼活体动态模型观察以及体外细胞3D培养等试验技术深入研究脑血管内皮细胞作用于GBM肿瘤细胞沿血管侵袭过程的机制并探索不同侵袭方式与病人预后的关系。