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.
Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
Oncogene. 2019 Oct;38(43):6898-6912. doi: 10.1038/s41388-019-0903-6. Epub 2019 Aug 9.
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.
血管周龛在神经胶质瘤中对于神经胶质瘤干细胞（GSCs）的维持至关重要，肿瘤内皮细胞（EC）之间的通讯以不完全了解的方式影响肿瘤发生。在这里，我们表明，与神经胶质瘤相关的人内皮细胞（GhECs），血管周龛的主要组成部分，释放细胞外囊泡（EVs），增加 GSC 的增殖和肿瘤球体的形成。用 GhEC-EVs 处理的 GSCs 在原位异种移植中比未处理的 GSCs 产生更大的肿瘤负担。对 EVs 内容的机制分析确定 CD9 是对 GSCs 影响的介质。CD9 可以激活 GSCs 中的 BMX/STAT3 信号通路。我们的结果通过鉴定在细胞间通讯过程中 EC 衍生的 EVs 转移 CD9，从而通过特异性维持 GSCs 来增强胶质母细胞瘤的侵袭性，阐明了 ECs 的肿瘤支持作用。
