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

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.

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。

本项研究通过生物3D打印的方式，针对GBM体外3D侵袭模型进行了有效的构建研究。.研究设计了一种GBM体外三维侵袭模型，采用真实大脑成分混合打印HA水凝胶与神经胶质细胞的混合水凝胶，探讨了各种生物墨水配比的可打印性，优化了打印参数，成功打印出模拟大脑的微环境。采用悬滴法构建GBM微肿瘤，通过比较基因组学的手段来探讨二维以及三维细胞共培养条件下GBM基因表达的差异性。希望从中能够找寻到与肿瘤构建三维结构以及肿瘤侵袭相关的基因。通过上述研究我们可以寻找到在细胞二维与三维培养中具有差异性的基因，对这部分基因进行进一步深入研究可以帮助我们更好的揭示GBM发生发展特别是形成肿瘤状三维结构以及侵袭生长的分子机制，为我们寻找到更好的治疗手段与药物靶点提供帮助。