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Glioma-derived miRNA-containing extracellular vesicles induce angiogenesis by reprogramming brain endothelial cells

Glioblastoma (GBM) is characterized by aberrant vascularization and a complex tumor microenvironment. The failure of anti-angiogenic therapies suggests pathways of GBM neovascularization, possibly attributable to glioblastoma stem cells (GSCs) and their interplay with the tumor microenvironment. It...

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Main Authors: Lucero, Rocco, Zappulli, Valentina, Sammarco, Alessandro, Murillo, Oscar D, Cheah, Pike See, Srinivasan, Srimeenakshi, Tai, Eric, Ting, David T., Wei, Zhiyun, Roth, Matthew E., Laurent, Louise C., Krichevsky, Anna M., Breakefield, Xandra O, Milosavljevic, Aleksandar
Format: Article
Language:English
Published: Cell Press 2020
Online Access:http://psasir.upm.edu.my/id/eprint/89124/1/CANCER.pdf
http://psasir.upm.edu.my/id/eprint/89124/
https://www.cell.com/cell-reports/fulltext/S2211-1247(20)30098-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS221112472030098X%3Fshowall%3Dtrue
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spelling my.upm.eprints.891242021-09-03T23:34:35Z http://psasir.upm.edu.my/id/eprint/89124/ Glioma-derived miRNA-containing extracellular vesicles induce angiogenesis by reprogramming brain endothelial cells Lucero, Rocco Zappulli, Valentina Sammarco, Alessandro Murillo, Oscar D Cheah, Pike See Srinivasan, Srimeenakshi Tai, Eric Ting, David T. Wei, Zhiyun Roth, Matthew E. Laurent, Louise C. Krichevsky, Anna M. Breakefield, Xandra O Milosavljevic, Aleksandar Glioblastoma (GBM) is characterized by aberrant vascularization and a complex tumor microenvironment. The failure of anti-angiogenic therapies suggests pathways of GBM neovascularization, possibly attributable to glioblastoma stem cells (GSCs) and their interplay with the tumor microenvironment. It has been established that GSC-derived extracellular vesicles (GSC-EVs) and their cargoes are proangiogenic in vitro. To further elucidate EV-mediated mechanisms of neovascularization in vitro, we perform RNA-seq and DNA methylation profiling of human brain endothelial cells exposed to GSC-EVs. To correlate these results to tumors in vivo, we perform histoepigenetic analysis of GBM molecular profiles in the TCGA collection. Remarkably, GSC-EVs and normal vascular growth factors stimulate highly distinct gene regulatory responses that converge on angiogenesis. The response to GSC-EVs shows a footprint of post-transcriptional gene silencing by EV-derived miRNAs. Our results provide insights into targetable angiogenesis pathways in GBM and miRNA candidates for liquid biopsy biomarkers. Cell Press 2020 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/89124/1/CANCER.pdf Lucero, Rocco and Zappulli, Valentina and Sammarco, Alessandro and Murillo, Oscar D and Cheah, Pike See and Srinivasan, Srimeenakshi and Tai, Eric and Ting, David T. and Wei, Zhiyun and Roth, Matthew E. and Laurent, Louise C. and Krichevsky, Anna M. and Breakefield, Xandra O and Milosavljevic, Aleksandar (2020) Glioma-derived miRNA-containing extracellular vesicles induce angiogenesis by reprogramming brain endothelial cells. Cell Reports, 30 (7). 2065 - 2074. ISSN 2211-1247 https://www.cell.com/cell-reports/fulltext/S2211-1247(20)30098-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS221112472030098X%3Fshowall%3Dtrue 10.1016/j.celrep.2020.01.073
institution Universiti Putra Malaysia
building UPM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Putra Malaysia
content_source UPM Institutional Repository
url_provider http://psasir.upm.edu.my/
language English
description Glioblastoma (GBM) is characterized by aberrant vascularization and a complex tumor microenvironment. The failure of anti-angiogenic therapies suggests pathways of GBM neovascularization, possibly attributable to glioblastoma stem cells (GSCs) and their interplay with the tumor microenvironment. It has been established that GSC-derived extracellular vesicles (GSC-EVs) and their cargoes are proangiogenic in vitro. To further elucidate EV-mediated mechanisms of neovascularization in vitro, we perform RNA-seq and DNA methylation profiling of human brain endothelial cells exposed to GSC-EVs. To correlate these results to tumors in vivo, we perform histoepigenetic analysis of GBM molecular profiles in the TCGA collection. Remarkably, GSC-EVs and normal vascular growth factors stimulate highly distinct gene regulatory responses that converge on angiogenesis. The response to GSC-EVs shows a footprint of post-transcriptional gene silencing by EV-derived miRNAs. Our results provide insights into targetable angiogenesis pathways in GBM and miRNA candidates for liquid biopsy biomarkers.
format Article
author Lucero, Rocco
Zappulli, Valentina
Sammarco, Alessandro
Murillo, Oscar D
Cheah, Pike See
Srinivasan, Srimeenakshi
Tai, Eric
Ting, David T.
Wei, Zhiyun
Roth, Matthew E.
Laurent, Louise C.
Krichevsky, Anna M.
Breakefield, Xandra O
Milosavljevic, Aleksandar
spellingShingle Lucero, Rocco
Zappulli, Valentina
Sammarco, Alessandro
Murillo, Oscar D
Cheah, Pike See
Srinivasan, Srimeenakshi
Tai, Eric
Ting, David T.
Wei, Zhiyun
Roth, Matthew E.
Laurent, Louise C.
Krichevsky, Anna M.
Breakefield, Xandra O
Milosavljevic, Aleksandar
Glioma-derived miRNA-containing extracellular vesicles induce angiogenesis by reprogramming brain endothelial cells
author_facet Lucero, Rocco
Zappulli, Valentina
Sammarco, Alessandro
Murillo, Oscar D
Cheah, Pike See
Srinivasan, Srimeenakshi
Tai, Eric
Ting, David T.
Wei, Zhiyun
Roth, Matthew E.
Laurent, Louise C.
Krichevsky, Anna M.
Breakefield, Xandra O
Milosavljevic, Aleksandar
author_sort Lucero, Rocco
title Glioma-derived miRNA-containing extracellular vesicles induce angiogenesis by reprogramming brain endothelial cells
title_short Glioma-derived miRNA-containing extracellular vesicles induce angiogenesis by reprogramming brain endothelial cells
title_full Glioma-derived miRNA-containing extracellular vesicles induce angiogenesis by reprogramming brain endothelial cells
title_fullStr Glioma-derived miRNA-containing extracellular vesicles induce angiogenesis by reprogramming brain endothelial cells
title_full_unstemmed Glioma-derived miRNA-containing extracellular vesicles induce angiogenesis by reprogramming brain endothelial cells
title_sort glioma-derived mirna-containing extracellular vesicles induce angiogenesis by reprogramming brain endothelial cells
publisher Cell Press
publishDate 2020
url http://psasir.upm.edu.my/id/eprint/89124/1/CANCER.pdf
http://psasir.upm.edu.my/id/eprint/89124/
https://www.cell.com/cell-reports/fulltext/S2211-1247(20)30098-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS221112472030098X%3Fshowall%3Dtrue
_version_ 1710677164902318080
score 13.211869

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