RhoA/ROCK信号途径在Sema4D介导的肺癌血管生成拟态形成中的作用及机制研究

项目名称： RhoA/ROCK信号途径在Sema4D介导的肺癌血管生成拟态形成中的作用及机制研究

项目编号： No.81201849

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 朱芳

作者单位： 华中科技大学

项目金额： 23万元

中文摘要： 血管生成拟态（VM）为肿瘤中一种全新的特殊血供模式，与目前抗血管生成治疗疗效不佳密切相关。肿瘤细胞自身变形为VM形成的关键步骤，RhoA/ROCK作为细胞骨架重组的关键调节因子，在肺癌细胞自身变形形成VM过程中的作用尚不明确。研究表明，RhoA通过调节细胞骨架促进内皮细胞迁移，在轴突导向因子Sema4D与内皮细胞上受体plexinB1结合促进的内皮依赖性血管新生中起重要作用。我们前期研究表明Sema4D与plexinB1在部分肺癌组织中同时高表达且与肺癌VM形成正相关。鉴于以上因素，我们推测，RhoA/ROCK可能通过调节肺癌细胞骨架促进细胞自身变形在Sema4D介导的肺癌VM形成中起重要作用。本研究拟以三维细胞培养和裸鼠移植瘤技术创建肺癌VM体内外模型，应用药物干预及siRNA技术探索RhoA/ROCK信号途径在Sema4D介导的肺癌VM形成中的作用及机制，为阻断肺癌血供治疗寻求新靶点。

中文关键词： 非小细胞肺癌；血管生成拟态；轴突导向因子sema4D；RhoA/ROCK信号通路；

英文摘要： Vasculogenic mimicry(VM) is a novel pattern of blood supply in tumor which is associated with the poor response of anti-angiogenesis treatment in lung cancer. The plasticity of malignant tumor cells is an important element of VM. RhoA/ROCK is a key factor of remodeling cell cytoskeleton. However the role and mechanism of RhoA/ROCK in the formation of VM in lung cancer remains unclear. It was reported that RhoA played a critical role in angiogenesis mediated by axon guidance factor semaphorin4D and its receptor plexinB1 through coordinating the cytoskeleton of endothelial cell and promoting endothelial cell motility. Our previous study confirmed that the expression of Sema4D and plexinB1 were higher than that in normal tissue and the high expression of Sema4D was related to the formation of VM in lung cancer. It is postulated that RhoA/ROCK signalling pathway may play an important role in the formation of VM mediated by Sema4D in lung cancer by regulating the cytoskeleton of lung cancer cells. In this study, we will set up the model of VM in lung cancer in vitro by culturing lung cancer cells in 3-dimensional cell cultures and in vivo by transplanting lung cancer cells in nude mice. Then, we will explore the effect and mechanism of RhoA/ROCK in the formation of VM mediated by Sema4D in lung cancer by gene silenci

英文关键词： Non-small cell lung carcinoma；Vasculogenic mimicry；Axon guidance factor sema4D；RhoA/ROCK signaling pathway；