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; Department of Neurosurgery, Hospital of Eighty-first Army Group of Chinese PLA, Zhang Jiakou, 075000, China.
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.
Cancer Lett. 2019 Dec 1;466:1-12. doi: 10.1016/j.canlet.2019.09.004. Epub 2019 Sep 12.
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.
复发性脑胶质瘤常发生在脑室下区（SVZ）附近，而神经干细胞（NSCs）就存在于 SVZ 区，据报道，脑胶质瘤衍生的细胞外囊泡（EVs）在肿瘤微环境中发挥重要作用，但具体细节尚不清楚。在这里，我们研究了 NSCs 是否参与脑胶质瘤衍生 EVs 介导的脑胶质瘤复发。我们通过向 NSCs 培养系统中添加脑胶质瘤衍生的 EVs 来研究 NSCs 的变化，发现 NSCs 分化为一种促进肿瘤的细胞。通过 CCK-8、划痕愈合和软琼脂克隆形成试验分别发现，这些转化细胞具有明显的增殖活性、高迁移率和克隆形成能力。体内试验表明，这些细胞可以加速裸鼠中 Ln229 细胞的肿瘤形成。此外，为了探讨 NSC 转化的机制，进行了单细胞转录组测序；我们的结果表明，S100B、CXCL14、EFEMP1、SCRG1、GLIPR1、HMGA1 和 CD44 等几个关键基因以及失调的信号通路可能对 NSCs 的转化很重要。这也表明 NSCs 可能通过脑胶质瘤释放 EV 参与脑胶质瘤的复发。这项工作有助于阐明手术后短时间内发生的脑胶质瘤复发的机制，并有助于寻找治疗这种疾病的新方法。
