Glioma-Derived miRNA-Containing Extracellular Vesicles Induce Angiogenesis by Reprogramming Brain Endothelial Cells | Zendy

Rocco Lucero | Zendy; Valentina Zappulli | Zendy; Alessandro Sammarco | Zendy; Oscar Murillo | Zendy; Pike-See Cheah | Zendy; Srimeenakshi Srinivasan | Zendy; Eric C. Tai | Zendy; David T. Ting | Zendy; Zhiyun Wei | Zendy; Matthew E. Roth | Zendy; Louise C. Laurent | Zendy; Anna M. Krichevsky | Zendy; Xandra O. Breakefield | Zendy; Aleksandar Milosavljevic | Zendy

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Glioma-Derived miRNA-Containing Extracellular Vesicles Induce Angiogenesis by Reprogramming Brain Endothelial Cells

Author(s) -

Rocco Lucero,

Valentina Zappulli,

Alessandro Sammarco,

Oscar Murillo,

Pike-See Cheah,

Srimeenakshi Srinivasan,

Eric C. Tai,

David T. Ting,

Zhiyun Wei,

Matthew E. Roth,

Louise C. Laurent,

Anna M. Krichevsky,

Xandra O. Breakefield,

Aleksandar Milosavljevic

Publication year - 2020

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2020.01.073

Subject(s) - angiogenesis , reprogramming , biology , microrna , glioma , cancer research , neovascularization , microvesicles , gene silencing , microbiology and biotechnology , tumor microenvironment , dna methylation , gene , gene expression , genetics , tumor 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 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.

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