胶质母细胞瘤相关的小胶质细胞重编程由细胞外 miR-21 的功能转移介导。

Glioblastoma-Associated Microglia Reprogramming Is Mediated by Functional Transfer of Extracellular miR-21.

机构信息

Departments of Neurology and Radiology, Massachusetts General Hospital, and NeuroDiscovery Center, Harvard Medical School, Boston, MA 02129, USA.

Department of Neurosurgery, UMC Utrecht Brain Center, University Medical Center, Utrecht University, 3584 CX Utrecht, the Netherlands.

出版信息

Cell Rep. 2019 Sep 17;28(12):3105-3119.e7. doi: 10.1016/j.celrep.2019.08.036.

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.

神经胶质瘤是原发性、弥漫浸润性脑肿瘤。小胶质细胞是中枢神经系统中的固有免疫细胞，构成了肿瘤块的很大一部分。神经胶质瘤细胞塑造其微环境，与周围细胞进行交流并重新编程，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相互沟通，部分是通过释放细胞外囊泡（EVs）。将稳定表达棕榈酰化 GFP 的小鼠神经胶质瘤细胞植入同种型 miR-21 缺失小鼠的颅内，用于标记 EVs。在这里，我们证明了 miR-21 的功能传递，在摄取肿瘤衍生的 EV 后，在小胶质细胞中调节特定的下游 mRNA 靶标。这些发现证明了在基于体内模型的研究中，EV 依赖性 microRNA 传递，并深入了解肿瘤细胞对小胶质细胞的重新编程，以创建有利于癌症进展的微环境。