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Glioma cells escaped from cytotoxicity of temozolomide and vincristine by communicating with human astrocytes

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A Correction to this article was published on 24 August 2021

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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.

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Acknowledgments

This project is supported by Grants from the National Natural Science Foundation of China (81172404, 81372720), the Shandong Provincial Outstanding Medical Academic Professional Program and the Special Foundation for Taishan Scholars (ts20110814). The authors are grateful to Dr. Lei Zhao and Jintang Sun for FACS analysis, and Zhong Yao, Ming Liu and Yang Xu for human glioma specimen collection.

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Authors and Affiliations

  1. Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, 250012, China

    Weiliang Chen, Donghai Wang, Songyu Chen, Bin Huang, Anjing Chen, Peng Zhao & Xingang Li

  2. Institute of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, China

    Weiliang Chen, Ying He, Songyu Chen, Qianqian Shao, Chao Ma & Xun Qu

  3. Department of Pediatric Surgery, Laizhou People’s Hospital, Yantai, China

    Xinwen Du

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  1. Weiliang Chen
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Correspondence to Xingang Li.

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Chen, W., Wang, D., Du, X. et al. Glioma cells escaped from cytotoxicity of temozolomide and vincristine by communicating with human astrocytes. Med Oncol 32, 43 (2015). https://doi.org/10.1007/s12032-015-0487-0

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