Angiocrine extracellular vesicles impose mesenchymal reprogramming upon proneural glioma stem cells

Lata Adnani, Jordan Kassouf, Brian Meehan, Cristiana Spinelli, Nadim Tawil, Ichiro Nakano and Janusz Rak ()
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Lata Adnani: Research Institute of the McGill University Health Centre
Jordan Kassouf: McGill University
Brian Meehan: Research Institute of the McGill University Health Centre
Cristiana Spinelli: Research Institute of the McGill University Health Centre
Nadim Tawil: Research Institute of the McGill University Health Centre
Ichiro Nakano: Hokuto Hospital
Janusz Rak: Research Institute of the McGill University Health Centre

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract Glioblastoma (GBM) is an incurable form of primary astrocytic brain tumor driven by glioma stem cell (GSC) compartment closely associated with the vascular niche. GSC phenotypes are heterogeneous and range from proneural to mesenchymal-like, the latter characterised by greater invasiveness. Here we document the secretory (angiocrine) role of endothelial cells and their derived extracellular vesicles (EVs) as drivers of proneural-to-mesenchymal reprogramming of GSCs. These changes involve activation of matrix metalloproteinases (MMPs) and NFκB, and inactivation of NOTCH, while altering responsiveness to chemotherapy and driving infiltrative growth in the brain. Our findings suggest that EV-mediated angiocrine interactions impact the nature of cellular stemness in GBM with implications for disease biology and therapy.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33235-7

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DOI: 10.1038/s41467-022-33235-7

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