title: Glioma cells escaped from cytotoxicity of temozolomide and vincristine by communicating with human astrocytes.
abstract: Resistance to chemotherapeutic drugs remains a great obstacle to successful treatment of gliomas. Understanding the mechanism of glioma chemoresistance is conducive to develop effective strategies to overcome resistance. Astrocytes are the major stromal cells in the brain and have been demonstrated to play a key role in the malignant phenotype of gliomas. However, little is known regarding its role in glioma chemoresistance. In our study, we established a co-culture system of human astrocytes and glioma in vitro to simulate tumor microenvironment. Our results showed that astrocytes significantly reduced glioma cell apoptosis induced by the chemotherapeutic drugs temozolomide and vincristine. This protective effect was dependent on direct contact between astrocytes and glioma cells through Cx43-GJC. Moreover, in human glioma specimens, we found astrocytes infiltrating around the tumor, with a reactive appearance, suggesting that these astrocytes would play the same chemoprotective effect on gliomas in vivo. Our results expand the understanding of the interaction between astrocytes and glioma cells and provide a possible explanation for unsatisfactory clinical outcomes of chemotherapeutic drugs. Cx43-GJC between astrocytes and glioma cells may be a potential target for overcoming chemoresistance in gliomas clinically.
authors: Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, 250012, China.
authors: Weiliang
authors: W
authors: Chen
authors: Donghai
authors: D
authors: Wang
authors: Xinwen
authors: X
authors: Du
authors: Ying
authors: Y
authors: He
authors: Songyu
authors: S
authors: Chen
authors: Qianqian
authors: Q
authors: Shao
authors: Chao
authors: C
authors: Ma
authors: Bin
authors: B
authors: Huang
authors: Anjing
authors: A
authors: Chen
authors: Peng
authors: P
authors: Zhao
authors: Xun
authors: X
authors: Qu
authors: Xingang
authors: X
authors: Li
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000378:metabolism*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication; D018920:Coculture Techniques; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D017629:Gap Junctions / Q000187:drug effects; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D000077204:Temozolomide; D059016:Tumor Microenvironment; D014750:Vincristine / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D018031:Connexin 43; D014750:Vincristine; D003606:Dacarbazine; D002118:Calcium; D000077204:Temozolomide
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