Glioblastoma-Associated Microglia Reprogramming Is Mediated by Functional Transfer of Extracellular miR-21
Glioblastoma-Associated Microglia Reprogramming Is Mediated by Functional Transfer of Extracellular miR-21
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DOI：
10.1016/j.celrep.2019.08.036
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发表时间：
2019-09-17
期刊：
影响因子：
8.8
通讯作者：
Breakefield, Xandra O.
中科院分区：
文献类型：
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作者：
Abels, Erik R.;Maas, Sybren L. N.;Breakefield, Xandra O.
神经胶质瘤是原发性、弥漫性浸润性脑肿瘤。小胶质细胞是CNS中的先天性免疫细胞，并且构成肿瘤块的相当大的一部分。胶质瘤细胞塑造其微环境，与周围细胞沟通并重新编程，导致血管生成增强，免疫抑制和细胞外基质重塑。神经胶质瘤细胞与小胶质细胞沟通，部分通过释放细胞外囊泡（EV）。将稳定表达棕榈酰化GFP以标记EV的小鼠神经胶质瘤细胞颅内植入同基因miR-21缺失小鼠中。在这里，我们证明了miR-21的功能性递送，在摄取肿瘤衍生的EV后调节小胶质细胞中的特定下游mRNA靶点。这些发现证明了在基于体内的模型中研究的EV依赖性microRNA递送，并提供了对肿瘤细胞重新编程小胶质细胞以创造有利于癌症进展的微环境的见解。
Gliomas are primary, diffusely infiltrating brain tumors. Microglia are innate immune cells in the CNS and make up a substantial portion of the tumor mass. Glioma cells shape their microenvironment, communicating with and reprogramming surrounding cells, resulting in enhanced angiogenesis, immune suppression, and remodeling of the extracellular matrix. Glioma cells communicate with microglia, in part by releasing extracellular vesicles (EVs). Mouse glioma cells stably expressing a palmitoylated GFP to label EVs were implanted intracranially into syngeneic miR-21-null mice. Here, we demonstrate functional delivery of miR-21, regulating specific downstream mRNA targets in microglia after uptake of tumor-derived EVs. These findings attest to EV-dependent microRNA delivery as studied in an in vivo-based model and provide insight into the reprograming of microglial cells by tumor cells to create a favorable microenvironment for cancer progression.