胶质母细胞瘤侵袭迁移的特性是其不良预后的主要原因，在前期研究基础上，我们提出：胶质瘤细胞沿着脑白质纤维束进行迁移及向微血管旁niche聚集需趋向信号引导，在微血管旁niche完成增殖-运动之间的表型转换和迁移接力。本项目拟对人及鼠脑胶质瘤沿迁移路径行系列取材及镜像切片，hMena、CD133、CD34、LFB、GM-130分别标记运动的肿瘤细胞、肿瘤干细胞、微血管、白质纤维、高尔基体，研究肿瘤细胞在白质中的迁移模式，并应用免疫组化、蛋白印迹杂交、RT-PCR技术，分析CXCL12/CXCR4在迁移路径中及微血管旁niche中的表达特点，判定迁移中增殖和运动细胞表型转换及miR451的开关作用；在鼠脑片模型中进行关键环节的体外分解研究。给予Rac1或(和)RhoA抑制剂，在体外及鼠脑胶质母细胞瘤模型中，观察抗细胞运动的靶向治疗效果。项目将为阐明恶性胶质瘤侵袭机理和抗侵袭靶向治疗提供新线索。

The characteristics of invasion and migration are the major cause for the poor prognosis of glioblastoma. Based upon our previous studies, we hypothesize that the chemotactic guidance would be required during the tumor cells migration along white matter fibers and their congregation to the microvascular niche in the white matter. The tumor cells in the routes to and aligning around microvascular niche would convert their phenotypes between proliferation and motility, thereafter migrate further in the white matter. In this study，we intend to study the invasion and migration patterns of malignant glioma cells in the white matter by serial collection of tissue samples along tumor migration routes and mirrow sections preparation as well. hMena, CD133,CD34,LFB and GM-130 will be labled to indicate tumor cells in motility, tumor stem cells, microvessels, white matter fibers and Golgi bodies respectively. Immnohistologic staining, western blot, and RT-PCR are employed to analyze the CXCL12/CXCR4 expression along the migration routes and arround the microvascular niche, while the phenotype conversion between proliferation and motility as well as the switch function of miR451 in the conversion are defined. The key experiments above will be repeated in the invasion model of rat brain slices in vitro to decompose the invasion mechanism hypothesized in this project. The effect of anti-migration targeted therapy for glioblastoma will be observed after administration of Rac1or (and) RhoA inhibition agents in the invasion models in vitro and orthotopic implanted model in rats. This research is expected to help us to understand invasion mechanisms of malignant glioma better and supply new clues for anti-invastion therapy for the tumor.