星形胶质细胞与胶质母细胞瘤侵袭生长的相关性及其调控机理的研究

Astrocytes are specialized immunological cells in CNS, possessing various types of immune functions. Our group confirmed that IL-17 positively functioned in IL-6 signaling in astrocytes as a positive feedback regulator, which might be one of the mechanisms of the astrocytes involved in the CNS immune system. However, up to state not much was known regarding the relation between astrocytes and the invasiveness of glial cells. We investigated the effects of astrocytes on the invasiveness related genes in glial cells at gene and protein levels and confirmed the role of astrocytes in tumor cell proliferation and invasiveness in vitro. Additionally, we determined the role of important signaling pathways involved in glioma growth, such as NF-κB and STAT-3 signalings, and proved the results by using specific inhibitors of NF-κB, STAT-3 and MAPK pathways. Moreover, ChIP analysis was done to detect the proteins which associated with the gene promoters. Our result provides evidence for further elucidating the role of immune responses in tumor growth, thereby to further understand the possible effect of astrocytes on tumor growth and invasiveness and the underlying mechanism, offering novel theoretical and experimental data for specifically targeting tumor growth in glioma.

星形胶质细胞是脑内特化的免疫细胞，具有多种免疫功能。我们课题组已经证实IL-17可以正向调节星形胶质细胞IL-6的正反馈通路，这可能是星形胶质细胞参与中枢神经系统免疫过程的机制之一。本课题拟从基因水平和蛋白水平研究星形胶质细胞对胶质母细胞瘤细胞系肿瘤侵袭性生长相关基因表达的作用，并在细胞功能水平明确星形胶质细胞对肿瘤细胞增殖、侵袭性的影响；检测NF-κB和STAT-3等肿瘤侵袭生长相关的重要信号传导通路的活性并应用信号传导通路抑制剂抑制NF-κB、STAT-3通路的作用以验证Western blot的实验结果；ChIP技术检测肿瘤侵袭性生长相关基因中启动序列中信号传导通路蛋白作用位点，从而明确星形胶质细胞与胶质母细胞瘤侵袭生长的相关性及其作用机理。本研究的结果可望加深对胶质瘤的生长及侵袭机理的认识，并为脑胶质瘤的分子靶向治疗及免疫治疗提供新的理论依据。

星形胶质细胞是脑内特化的免疫细胞，具有多种免疫功能。我们课题组已经证实IL-17可以正向调节星形胶质细胞IL-6的正反馈通路，这可能是星形胶质细胞参与中枢神经系统免疫过程的机制之一。本课题从基因水平和蛋白水平研究星形胶质细胞对胶质母细胞瘤细胞系肿瘤侵袭性生长相关基因表达的作用，并在细胞功能水平明确星形胶质细胞对肿瘤细胞增殖、侵袭性的影响；检测NF-κB和STAT-3等肿瘤侵袭生长相关的重要信号传导通路的活性并应用信号传导通路抑制剂抑制NF-κB、STAT-3通路的作用以验证Western blot的实验结果；特别是我们研究了PD-L1基因在胶质瘤标本中的表达情况，并且发现PD-L1基因的表达与胶质瘤的预后密切相关，本研究的结果可望加深对胶质瘤的生长及侵袭机理的认识，并为脑胶质瘤的分子靶向治疗及免疫治疗提供新的理论依据。