Glioblastoma-associated microglia reprogramming is mediated by functional transfer of extracellular miR-21

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 su...

Full description

Bibliographic Details
Main Authors: Abels, Erik R., Maas, Sybren L. N., Nieland, Lisa, Wei, Zhiyun, Cheah, Pike See, Tai, Eric, Kolsteeg, Christy-Joy, Dusoswa, Sophie A., Ting, David T., Hickman, Suzanne, El Khoury, Joseph, Krichevsky, Anna M., Broekman, Marike L. D., Breakefield, Xandra O.
Format: Article
Published: Cell Press 2019
_version_ 1796980707473489920
author Abels, Erik R.
Maas, Sybren L. N.
Nieland, Lisa
Wei, Zhiyun
Cheah, Pike See
Tai, Eric
Kolsteeg, Christy-Joy
Dusoswa, Sophie A.
Ting, David T.
Hickman, Suzanne
El Khoury, Joseph
Krichevsky, Anna M.
Broekman, Marike L. D.
Breakefield, Xandra O.
author_facet Abels, Erik R.
Maas, Sybren L. N.
Nieland, Lisa
Wei, Zhiyun
Cheah, Pike See
Tai, Eric
Kolsteeg, Christy-Joy
Dusoswa, Sophie A.
Ting, David T.
Hickman, Suzanne
El Khoury, Joseph
Krichevsky, Anna M.
Broekman, Marike L. D.
Breakefield, Xandra O.
author_sort Abels, Erik R.
collection UPM
description 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.
first_indexed 2024-03-06T10:27:01Z
format Article
id upm.eprints-79998
institution Universiti Putra Malaysia
last_indexed 2024-03-06T10:27:01Z
publishDate 2019
publisher Cell Press
record_format dspace
spelling upm.eprints-799982023-05-30T08:42:51Z http://psasir.upm.edu.my/id/eprint/79998/ Glioblastoma-associated microglia reprogramming is mediated by functional transfer of extracellular miR-21 Abels, Erik R. Maas, Sybren L. N. Nieland, Lisa Wei, Zhiyun Cheah, Pike See Tai, Eric Kolsteeg, Christy-Joy Dusoswa, Sophie A. Ting, David T. Hickman, Suzanne El Khoury, Joseph Krichevsky, Anna M. Broekman, Marike L. D. Breakefield, Xandra O. 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. Cell Press 2019 Article PeerReviewed Abels, Erik R. and Maas, Sybren L. N. and Nieland, Lisa and Wei, Zhiyun and Cheah, Pike See and Tai, Eric and Kolsteeg, Christy-Joy and Dusoswa, Sophie A. and Ting, David T. and Hickman, Suzanne and El Khoury, Joseph and Krichevsky, Anna M. and Broekman, Marike L. D. and Breakefield, Xandra O. (2019) Glioblastoma-associated microglia reprogramming is mediated by functional transfer of extracellular miR-21. Cell Reports, 28 (12). pp. 3105-3119. ISSN 2211-1247 https://www.sciencedirect.com/science/article/pii/S2211124719310769?via%3Dihub 10.1016/j.celrep.2019.08.036
spellingShingle Abels, Erik R.
Maas, Sybren L. N.
Nieland, Lisa
Wei, Zhiyun
Cheah, Pike See
Tai, Eric
Kolsteeg, Christy-Joy
Dusoswa, Sophie A.
Ting, David T.
Hickman, Suzanne
El Khoury, Joseph
Krichevsky, Anna M.
Broekman, Marike L. D.
Breakefield, Xandra O.
Glioblastoma-associated microglia reprogramming is mediated by functional transfer of extracellular miR-21
title Glioblastoma-associated microglia reprogramming is mediated by functional transfer of extracellular miR-21
title_full Glioblastoma-associated microglia reprogramming is mediated by functional transfer of extracellular miR-21
title_fullStr Glioblastoma-associated microglia reprogramming is mediated by functional transfer of extracellular miR-21
title_full_unstemmed Glioblastoma-associated microglia reprogramming is mediated by functional transfer of extracellular miR-21
title_short Glioblastoma-associated microglia reprogramming is mediated by functional transfer of extracellular miR-21
title_sort glioblastoma associated microglia reprogramming is mediated by functional transfer of extracellular mir 21
work_keys_str_mv AT abelserikr glioblastomaassociatedmicrogliareprogrammingismediatedbyfunctionaltransferofextracellularmir21
AT maassybrenln glioblastomaassociatedmicrogliareprogrammingismediatedbyfunctionaltransferofextracellularmir21
AT nielandlisa glioblastomaassociatedmicrogliareprogrammingismediatedbyfunctionaltransferofextracellularmir21
AT weizhiyun glioblastomaassociatedmicrogliareprogrammingismediatedbyfunctionaltransferofextracellularmir21
AT cheahpikesee glioblastomaassociatedmicrogliareprogrammingismediatedbyfunctionaltransferofextracellularmir21
AT taieric glioblastomaassociatedmicrogliareprogrammingismediatedbyfunctionaltransferofextracellularmir21
AT kolsteegchristyjoy glioblastomaassociatedmicrogliareprogrammingismediatedbyfunctionaltransferofextracellularmir21
AT dusoswasophiea glioblastomaassociatedmicrogliareprogrammingismediatedbyfunctionaltransferofextracellularmir21
AT tingdavidt glioblastomaassociatedmicrogliareprogrammingismediatedbyfunctionaltransferofextracellularmir21
AT hickmansuzanne glioblastomaassociatedmicrogliareprogrammingismediatedbyfunctionaltransferofextracellularmir21
AT elkhouryjoseph glioblastomaassociatedmicrogliareprogrammingismediatedbyfunctionaltransferofextracellularmir21
AT krichevskyannam glioblastomaassociatedmicrogliareprogrammingismediatedbyfunctionaltransferofextracellularmir21
AT broekmanmarikeld glioblastomaassociatedmicrogliareprogrammingismediatedbyfunctionaltransferofextracellularmir21
AT breakefieldxandrao glioblastomaassociatedmicrogliareprogrammingismediatedbyfunctionaltransferofextracellularmir21