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Glioblastoma extracellular vesicles induce the tumour-promoting transformation of neural stem cells

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机构: [a]Department of Neurosurgery, Chinese People's Liberation Army of China (PLA) General Hospital, Medical School of Chinese PLA, Institute of Neurosurgery of Chinese PLA, Beijing, 100853, China [b]Department of Neurosurgery, Hospital of Eighty-first Army Group of Chinese PLA, Zhang Jiakou, 075000, China [c]Department of Medicine, Surgery, and Cell Biology, The University of Oklahoma Health Sciences Center, Stanton L. Young Biomedical Research Center, Oklahoma City, OK, 73104, USA [d]Department of Cell Biology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China [e]Department of Pathology, Hospital of Eighty-first Army Group of Chinese PLA, Zhang Jiakou, 075000, China [f]Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, 110122, China
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关键词: Extracellular vesicles Glioblastoma Neural stem cells Single cell sequencing

摘要:
Recurrent glioblastomas are frequently found near subventricular zone (SVZ) areas of the brain where neural stem cells (NSCs) reside, and glioblastoma-derived extracellular vesicles (EVs) are reported to play important roles in tumour micro-environment, but the details are not clear. Here, we investigated the possibility that NSCs are involved in glioblastoma relapse mediated by glioblastoma-derived EVs. We studied changes to NSCs by adding glioblastoma-derived EVs into a culture system of NSCs, and found that NSCs differentiated into a type of tumour-promoting cell. These transformed cells had distinguished proliferation activity, a high migration rate, and clone-forming ability revealed by CCK-8, wound healing and soft agar clone formation assays, respectively. In vivo assays indicated that these cells could accelerate tumour formation by Ln229 cells in nude mice. Moreover, to explore the mechanisms underlying NSC transformation, single cell transcriptome sequencing was performed; our results suggest that several key genes such as S100B, CXCL14, EFEMP1, SCRG1, GLIPR1, HMGA1 and CD44 and dysregulated signalling may be important for the transformation of NSCs. It is also indicated that NSCs may be involved in glioblastoma recurrence through EV release by glioblastoma in this work. This could help to illuminate the mechanism of glioblastoma relapse, which occurs in a brief period after surgical excision, and contribute to finding new ways to treat this disease. © 2019 Elsevier B.V.

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出版当年[2018]版:
大类 | 1 区 医学
小类 | 2 区 肿瘤学
最新[2025]版:
大类 | 1 区 医学
小类 | 2 区 肿瘤学
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Q1 ONCOLOGY
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Q1 ONCOLOGY

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第一作者机构: [a]Department of Neurosurgery, Chinese People's Liberation Army of China (PLA) General Hospital, Medical School of Chinese PLA, Institute of Neurosurgery of Chinese PLA, Beijing, 100853, China [b]Department of Neurosurgery, Hospital of Eighty-first Army Group of Chinese PLA, Zhang Jiakou, 075000, China
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通讯机构: [a]Department of Neurosurgery, Chinese People's Liberation Army of China (PLA) General Hospital, Medical School of Chinese PLA, Institute of Neurosurgery of Chinese PLA, Beijing, 100853, China [f]Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, 110122, China
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