Survivin在低氧诱导喉癌淋巴管生成中的调控作用及其分子机制

项目名称： Survivin在低氧诱导喉癌淋巴管生成中的调控作用及其分子机制

项目编号： No.81502339

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 李大伟

作者单位： 上海交通大学

项目金额： 16万元

中文摘要： 淋巴道转移是人喉癌最常见的转移途径，而淋巴管生成是肿瘤发生淋巴道转移的关键步骤。研究证实，低氧微环境可诱导肿瘤淋巴管生成，但其分子调控机制尚未明确。我们前期研究发现，在人喉癌组织中，凋亡抑制蛋白survivin的表达与淋巴结转移率、淋巴管密度均呈正相关；低氧刺激可有效上调survivin在喉癌细胞中的表达。此外，既往研究及预实验结果提示，喉癌细胞中survivin与VEGF-C的表达之间可能存在双向的正调控关系。因此，我们推断，喉癌细胞中survivin可能通过某种信号转导途径与VEGF-C构成一个正反馈调控环路而调控VEGF-C的表达，参与介导低氧所诱导的喉癌淋巴管生成。本项目拟采用喉癌细胞的体内外研究，旨在阐明survivin在低氧诱导喉癌淋巴管生成中的调控作用，并探讨参与此调控过程的分子机制。本项目可为喉癌淋巴管生成的微环境调控机理提供理论补充，为靶向治疗喉癌提供实验依据。

中文关键词： 下咽；喉肿瘤；低氧；淋巴管生成；Survivin；；VEGF-C

英文摘要： Lymphatic metastasis has been regarded as a major route for the dissemination of human laryngeal cancer. Moreover, lymphangiogenesis is a critical step for lymphatic metastasis of tumor cells. Hypoxia, as an essential feature of the tumour microenvironment, could induce tumor lymphangiogenesis, but its mechanisms are still unclear. In our previous study, Survivin, as a member of the Inhibitor of Apoptosis proteins, has been confirmed that its expression is positive correlated with lymph node metastasis, lymphatic vessel density in human laryngeal cancer. Meanwhile, it has been shown that survivin expression in laryngeal cancer cells could be up-regulated by hypoxia. The literature reports and our prepare experiment suggested that there may be a two – way positive correlation between survivin and VEGF-C expression in human cancer cells. Thus, we deduce that survivin may form a positive feedback circuit with VEGF–C in laryngeal cancer cells to enhance VEGF-C expression and mediate hypoxia-induced lymphangiogenesis of laryngeal cancer. This study is to explore the role and mechanisms of survivin in hypoxia induced lymphangiogenesis of laryngeal cancer by using technology such as RNA interference, gene transfection both in vitro and in vivo. It is beneficial to provide the new theory for lymphatic metastasis of laryngeal cancer regulated by microenvironment, and provide experimental basis for targeted therapy of laryngeal cancer.

英文关键词： Laryngeal neoplasm;Hypoxia;Lymphangiogenesis;Survivin; VEGF-C