Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No.6 Tiantan Xili, Dongcheng District, Beijing, 100050, China.
Department of Neurology, University of Pittsburgh, S-598 South Biomedical Science Tower, 3500 Terrace St., Pittsburgh, PA, 15213, USA.
Mol Neurobiol. 2018 Aug;55(8):6927-6938. doi: 10.1007/s12035-018-0880-8. Epub 2018 Jan 23.
Despite the multidisciplinary integration in the therapeutic management of glioblastoma multiforme (GBM), the prognosis of GBM patients is poor. There is growing recognition that the cells in the tumor microenvironment play a vital role in regulating the progression of glioma. Astrocytes are an important component of the blood-brain barrier (BBB) as well as the tripartite synapse neural network to promote bidirectional communication with neurons under physiological conditions. Emerging evidence shows that tumor-associated reactive astrocytes interact with glioma cells and facilitate the progression, aggression, and survival of tumors by releasing different cytokines. Communication between reactive astrocytes and glioma cells is further promoted through ion channels and ion transporters, which augment the migratory capacity and invasiveness of tumor cells by modifying H and Ca concentrations and stimulating volume changes in the cell. This in part contributes to the loss of epithelial polarization, initiating epithelial-mesenchymal transition. Therefore, this review will summarize the recent findings on the role of reactive astrocytes in the progression of GBM and in the development of treatment-resistant glioma. In addition, the involvement of ion channels and transporters in bridging the interactions between tumor cells and astrocytes and their potential as new therapeutic anti-tumor targets will be discussed.
尽管在多学科综合治疗多形性胶质母细胞瘤（GBM）方面取得了进展，但 GBM 患者的预后仍然很差。人们越来越认识到，肿瘤微环境中的细胞在调节神经胶质瘤的进展中起着至关重要的作用。星形胶质细胞是血脑屏障（BBB）的重要组成部分，也是三突触神经网络的一部分，在生理条件下促进与神经元的双向通讯。新出现的证据表明，肿瘤相关的反应性星形胶质细胞与神经胶质瘤细胞相互作用，并通过释放不同的细胞因子促进肿瘤的进展、侵袭和存活。反应性星形胶质细胞和神经胶质瘤细胞之间的通讯通过离子通道和离子转运体进一步增强，通过改变 H 和 Ca 浓度并刺激细胞体积变化，增强肿瘤细胞的迁移能力和侵袭性。这在一定程度上导致上皮极性丧失，引发上皮-间充质转化。因此，本综述将总结近年来关于反应性星形胶质细胞在 GBM 进展和治疗耐药性神经胶质瘤发生中的作用的研究进展。此外，还将讨论离子通道和转运体在桥接肿瘤细胞和星形胶质细胞之间相互作用中的作用及其作为新的治疗抗肿瘤靶点的潜力。
