机构:[1]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No.6 Tiantan Xili, Dongcheng District, Beijing 100050, China重点科室诊疗科室神经外科神经外科首都医科大学附属天坛医院[2]Department of Neurology, University of Pittsburgh, S-598 South Biomedical Science Tower, 3500 Terrace St., Pittsburgh, PA 15213, USA[3]Chinese National Clinical Research Center for Neurological Diseases, Beijing, China[4]Lake Erie College of Osteopathic Medicine—Seton Hill, Greensburg, PA, USA[5]Beijing Neurosurgical Institute, Beijing, China研究所北京市神经外科研究所首都医科大学附属天坛医院[6]Veterans Affairs Pittsburgh Health Care System, Geriatric Research, Educational and Clinical Center, Pittsburgh, PA, USA
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 Ca2+ 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.
基金:
NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01NS75995]
第一作者机构:[1]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No.6 Tiantan Xili, Dongcheng District, Beijing 100050, China[2]Department of Neurology, University of Pittsburgh, S-598 South Biomedical Science Tower, 3500 Terrace St., Pittsburgh, PA 15213, USA[3]Chinese National Clinical Research Center for Neurological Diseases, Beijing, China
通讯作者:
通讯机构:[1]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No.6 Tiantan Xili, Dongcheng District, Beijing 100050, China[2]Department of Neurology, University of Pittsburgh, S-598 South Biomedical Science Tower, 3500 Terrace St., Pittsburgh, PA 15213, USA[3]Chinese National Clinical Research Center for Neurological Diseases, Beijing, China[5]Beijing Neurosurgical Institute, Beijing, China[6]Veterans Affairs Pittsburgh Health Care System, Geriatric Research, Educational and Clinical Center, Pittsburgh, PA, USA