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Glioma-associated human endothelial cell-derived extracellular vesicles specifically promote the tumourigenicity of glioma stem cells via CD9

Oncogene volume 38, pages 6898–6912 (2019)Cite this article

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A Correction to this article was published on 19 September 2019

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Abstract

The perivascular niche in glioma is critical for the maintenance of glioma stem cells (GSCs), and tumour-endothelial cell (EC) communication impacts tumourigenesis in ways that are incompletely understood. Here, we show that glioma-associated human endothelial cells (GhECs), a main component of the perivascular niche, release extracellular vesicles (EVs) that increase GSC proliferation and tumour-sphere formation. GSCs treated with GhEC-EVs create a significantly greater tumour burden than do untreated GSCs in orthotopic xenografts. Mechanistic, analysis of EVs content identified CD9 as a mediator of the effects on GSCs. CD9 can activate the BMX/STAT3 signalling pathway in GSCs. Our results illuminate the tumour-supporting role of ECs by identifying that EC-derived EVs transfer of CD9 during intercellular communication, thereby enhancing the aggressiveness of glioblastoma by specifically maintaining GSCs.

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  • 19 September 2019

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

  • 20 September 2019

    The original HTML and PDF versions of this Article were updated after publication to correct author affiliation errors.

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Acknowledgements

We thank the Department of Neurosurgery of Tiantan Hospital for providing glioma surgical specimens and the CGGA database.

Funding

The National Key Research and Development Program of China (2016YFC0902500, 2016YFC0902502 and 2016YFA0100702), and National Sciences Foundation of China (31671316, 31670789), CAMS Innovation Fund for Medical Sciences (CIFMS, 2016-I2M-1–001, 2016-I2M-2–001, 2016-I2M-1–004, 2017-I2M-2–004, 2017-I2M-3–010 and 2017-I2M-1–004).

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Authors and Affiliations

  1. State Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Medical Primate Research Center, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China

    Dengke Li, Yuan Tian, Yan Hu, Yingjiao Qi, Ningyu Tian, Shanshan Li, Peishan Hu, Qunfang Wei, Zhizhong Wei, Shanshan Wang, Bin Yin, Jiangang Yuan, Boqin Qiang, Wei Han & Xiaozhong Peng

  2. Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China

    Fan Wu & Tao Jiang

  3. Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Kunming, China

    Zhizhong Wei & Xiaozhong Peng

  4. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    Tao Jiang

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  1. Dengke Li
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Li, D., Tian, Y., Hu, Y. et al. Glioma-associated human endothelial cell-derived extracellular vesicles specifically promote the tumourigenicity of glioma stem cells via CD9. Oncogene 38, 6898–6912 (2019). https://doi.org/10.1038/s41388-019-0903-6

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