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

doi:10.1016/j.celrep.2019.08.036

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^*

^*Corresponding author for this work

Harvard Pilgrim Health Care Institute
Massachusetts General Hospital and Harvard Medical School
Amsterdam Institute for Infection and Immunology
NKI-AvL and Leiden University Medical Center
University Medical Centre Utrecht

Research output: Contribution to journal › Article › Academic › peer-review

175 Citations (Scopus)

17 Downloads (Pure)

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 language	English
Pages (from-to)	3105-3119.e7
Number of pages	23
Journal	Cell Reports
Volume	28
Issue number	12
DOIs	https://doi.org/10.1016/j.celrep.2019.08.036
Publication status	Published - 17 Sept 2019
Externally published	Yes

Bibliographical note

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1016/j.celrep.2019.08.036Licence: CC BY-NC-ND

PIIS2211124719310769Final published version, 3.93 MBLicence: CC BY-NC-ND

Cite this

Abels, E. R., Maas, S. L. N., Nieland, L., Wei, Z., Cheah, P. S., Tai, E., Kolsteeg, C.-J., Dusoswa, S. A., Ting, D. T., Hickman, S., El Khoury, J., Krichevsky, A. M., Broekman, M. L. D., & 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

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title = "Glioblastoma-Associated Microglia Reprogramming Is Mediated by Functional Transfer of Extracellular miR-21",

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.",

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

year = "2019",

month = sep,

day = "17",

doi = "10.1016/j.celrep.2019.08.036",

language = "English",

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Abels, ER, Maas, SLN, Nieland, L, Wei, Z, Cheah, PS, Tai, E, Kolsteeg, C-J, Dusoswa, SA, Ting, DT, Hickman, S, El Khoury, J, Krichevsky, AM, Broekman, MLD & Breakefield, XO 2019, 'Glioblastoma-Associated Microglia Reprogramming Is Mediated by Functional Transfer of Extracellular miR-21', Cell Reports, vol. 28, no. 12, pp. 3105-3119.e7. https://doi.org/10.1016/j.celrep.2019.08.036

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T1 - Glioblastoma-Associated Microglia Reprogramming Is Mediated by Functional Transfer of Extracellular miR-21

AU - Abels, Erik R

AU - Maas, Sybren L N

AU - Nieland, Lisa

AU - Wei, Zhiyun

AU - Cheah, Pike See

AU - Tai, Eric

AU - Kolsteeg, Christy-Joy

AU - Dusoswa, Sophie A

AU - Ting, David T

AU - Hickman, Suzanne

AU - El Khoury, Joseph

AU - Krichevsky, Anna M

AU - Broekman, Marike L D

AU - Breakefield, Xandra O

PY - 2019/9/17

Y1 - 2019/9/17

N2 - 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.

AB - 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.

U2 - 10.1016/j.celrep.2019.08.036

DO - 10.1016/j.celrep.2019.08.036

M3 - Article

C2 - 31533034

SN - 2211-1247

VL - 28

SP - 3105-3119.e7

JO - Cell Reports

JF - Cell Reports

IS - 12

ER -

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

Abstract

Bibliographical note

UN SDGs

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