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

被引：161

作者：

Abels, Erik R. ^{[1
,2
,3
]}

Maas, Sybren L. N. ^{[4
]}

Nieland, Lisa ^{[1
,2
,3
]}

Wei, Zhiyun ^{[5
]}

Cheah, Pike See ^{[1
,2
,3
,6
]}

Tai, Eric ^{[7
,8
]}

Kolsteeg, Christy-Joy ^{[1
,2
,3
]}

Dusoswa, Sophie A. ^{[9
,10
]}

Ting, David T. ^{[7
,8
]}

Hickman, Suzanne ^{[11
,12
]}

El Khoury, Joseph ^{[11
,12
]}

Krichevsky, Anna M. ^{[5
]}

Broekman, Marike L. D. ^{[13
,14
]}

Breakefield, Xandra O. ^{[1
,2
,3
]}

机构：

[1] Harvard Med Sch, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02129 USA

[2] Harvard Med Sch, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02129 USA

[3] Harvard Med Sch, NeuroDiscovery Ctr, Boston, MA 02129 USA

[4] Univ Utrecht, Univ Med Ctr, Dept Neurosurg, UMC Utrecht Brain Ctr, NL-3584 CX Utrecht, Netherlands

[5] Harvard Med Sch, Brigham & Womens Hosp, Dept Neurol, Ann Romney Ctr Neurol Dis, Boston, MA 02115 USA

[6] Univ Putra Malaysia, Dept Human Anat, Fac Med & Hlth Sci, Serdang, Selangor 43400, Malaysia

[7] Massachusetts Gen Hosp, Canc Ctr, Boston, MA 02114 USA

[8] Harvard Med Sch, Boston, MA 02114 USA

[9] Amsterdam UMC, Dept Mol Cell Biol & Immunol, Amsterdam Infect & Immunol Inst, NL-1081 HZ Amsterdam, Netherlands

[10] Amsterdam UMC, Canc Ctr Amsterdam, NL-1081 HZ Amsterdam, Netherlands

[11] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02129 USA

[12] Harvard Med Sch, Boston, MA 02129 USA

[13] Leiden Univ, Dept Neurosurg, Med Ctr, NL-2300 RC Leiden, Netherlands

[14] Haaglanden Med Ctr, Dept Neurosurg, NL-2512 VA The Hague, Netherlands

来源：

CELL REPORTS | 2019年 / 28卷 / 12期

关键词：

HUMAN-BRAIN TUMORS; MICRORNA EXPRESSION; LIVER-REGENERATION; MACROPHAGE CONTENT; STEM-CELLS; VESICLES; MIRNA-21; MOUSE; RNA; DIFFERENTIATION;

D O I：

10.1016/j.celrep.2019.08.036

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：3105 / +

页数：22

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