体外三维脑组织模型中胶质母细胞瘤侵袭机制的相关研究

项目名称： 体外三维脑组织模型中胶质母细胞瘤侵袭机制的相关研究

项目编号： No.81501607

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： 马梁

作者单位： 浙江大学

项目金额： 18万元

中文摘要： 胶质母细胞瘤（GBM）是恶性程度最高的神经胶质瘤，一直是我国恶性肿瘤治疗领域的重大挑战。GBM属于侵袭性生长模式，易于侵犯周围脑组织，造成术后复发风险高，研究和探索GBM的侵袭特性，掌握其发生、发展的分子机制，对于深入理解此类肿瘤的致命机理，指导药物开发和探索有效的肿瘤治疗手段具有极其重要的意义。然而长期以来，对于GBM侵袭性的认识缺乏合适的三维模型，严重制约了人们对其的认识。本项研究拟通过采用三维打印的手段来混合神经胶质细胞与透明质酸水凝胶，创造出一个模拟大脑的微环境，再将GBM微肿瘤移植到此模拟脑组织上，真实模拟大脑内GBM的侵袭过程。我们以此复杂三维体系为模型，研究GBM侵袭前后的基因变化，葡萄糖浓度梯度对GBM侵袭的诱导作用以及miR-127-3p在GBM侵袭过程中所起的调控作用，为揭示GBM侵袭性生长的分子机制奠定一定的理论基础，也为GBM侵袭性的研究提供新的工具和有效手段。

中文关键词： 神经胶质母细胞瘤；三维打印；脑组织模型；侵袭

英文摘要： Glioblastoma (GBM) is the most malignant glioma, has been a major challenge in the field of China’s treatment of cancer. GBM belongs to the invasive growth pattern, easy to invade surrounding brain tissue, resulting in high risk of postoperative recurrence, the research on the invasiveness characteristic of GBM, knowing the molecular mechanism of its occurrence and development can help us deeply understand the lethal mechanism of tumor, has the extremely significance to guide drug development and explore the effective therapy of tumor. But for a long time, the lack of suitable three-dimensional GBM invasion model seriously restricted our understanding. In this study we intend to use 3D printing means to mix glial cells and hyaluronic acid hydrogels, create a microenvironment mimic the brain, then transplant GBM micro tumor to brain tissue to simulate the invasion process. With this complex three-dimensional model system, we intend to study on GBM gene changes before and after the invasion, the glucose concentration gradient on the inducing effect of GBM and the regulation role of miR-127-3p on GBM invasion, lays the theoretical foundation for revealing the molecular mechanism of GBM invasive growth, provides new tools and effective means to study GBM invasion.

英文关键词： GBM ;3D printing;brain tissue model;invasion