VEGF调控胶质瘤血管生成拟态向肿瘤细胞源性血管过渡及其机制研究

Gliomas are highly angiogenic and characterized by microvascular proliferations. However, the clinical benefit of anti-blood vessel endothelium in glioblastoma remains unsatisfactory. A better understanding of glioma vascularization is needed to optimize anti-vascular therapy. In our pilot study we found that there were four types of microcirculation pattern existed in glioblastoma: endothelium dependent vessel, tumor cell dependent vessel, extracellular matrix (ECM) dependent vessel, and mosaic vessel. Our study also evidenced that VEGF regulates VM formation and the transition from vesculogenic mimicry to tumor-drived vessels. In this study, we design to dynamicly observe the detail process of VEGF regulating VM formation and the transition from vesculogenic mimicry to tumor-drived vessels by using the in vitro and in vivo models and expect to clarify the key cellular signal pathway by analysis of genome informatics using gene array. We will confirm a new mechanism of alternative glioma vascularization and open a new perspective for the antivascular treatment strategy.

胶质瘤是一种高度血管化的实体肿瘤，新生血管形成是胶质瘤增殖和侵袭的基础，而目前主要针对血管内皮细胞的抗血管生成临床治疗效果却不如人意，提示我们必须重新认识肿瘤血管生成的本质。前期研究中我们发现胶质母细胞瘤中存在拟态血管、马赛克血管、肿瘤细胞源性血管等多种微循环管道，同时还初步证实VEGF在这三种管道形成及演化过程中可能起到了关键的调控作用。本课题拟利用体内外血管生成模型观察VEGF促进拟态血管的形成并调控其向肿瘤血管演进的动态过程，采用激光捕获显微切割技术及基因信息学差异分析，明确具体的细胞调控通路，旨在阐明VEGF促进拟态血管形成并调控其向肿瘤血管演进的机制，为以血管生成拟态为靶点的从源头上阻断肿瘤血管生成治疗提供新的策略。

胶质瘤是一种高度血管化的实体肿瘤，新生血管形成是胶质瘤增殖和侵袭的基础，而目前主要针对血管内皮细胞的抗血管生成临床治疗效果却不如人意，提示我们必须重新认识肿瘤血管生成的本质。前期研究中我们发现胶质母细胞瘤中存在拟态血管、马赛克血管、肿瘤细胞源性血管等多种微循环管道，同时还初步证实VEGF在这三种管道形成及演化过程中可能起到了关键的调控作用。本课题通过临床胶质瘤标本获取原代胶质瘤干细胞，应用体外三维培养模型，采用体外动态细胞成像系统记录捕捉了胶质瘤干细胞向血管内皮细胞转化的动态过程及相应的分子事件，直观的证实部分胶质瘤微循环来自肿瘤干细胞本身的假设。应用转基因荧光裸鼠原位成瘤模型 采用体内荧光管道三维重建技术，重建了胶质瘤四种微循环管道构筑，为更好的理解胶质瘤养分供给系统提供参考。