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

Erik R. Abels, Sybren L. N. Maas, Lisa Nieland, Zhiyun Wei, Pike See Cheah, Eric Tai, Christy-Joy Kolsteeg, Sophie A. Dusoswa, David T. Ting, Suzanne Hickman, Joseph el Khoury, Anna M. Krichevsky, Marike L. D. Broekman, Xandra O. Breakefield

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)3105-3119.e7
JournalCell Reports
Volume28
Issue number12
DOIs
Publication statusPublished - 17 Sep 2019

Cite this

Abels, E. R., Maas, S. L. N., Nieland, L., Wei, Z., Cheah, P. S., Tai, E., ... Breakefield, X. O. (2019). Glioblastoma-Associated Microglia Reprogramming Is Mediated by Functional Transfer of Extracellular miR-21. Cell Reports, 28(12), 3105-3119.e7. https://doi.org/10.1016/j.celrep.2019.08.036