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

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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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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Correspondence to Wei Han or Xiaozhong Peng.

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