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Mesenchymal glioma stem cells trigger vasectasia—distinct neovascularization process stimulated by extracellular vesicles carrying EGFR

Author

Listed:
  • Cristiana Spinelli

    (The Research Institute of the McGill University Health Centre)

  • Lata Adnani

    (The Research Institute of the McGill University Health Centre)

  • Brian Meehan

    (The Research Institute of the McGill University Health Centre)

  • Laura Montermini

    (The Research Institute of the McGill University Health Centre)

  • Sidong Huang

    (McGill University
    McGill University)

  • Minjun Kim

    (McGill University)

  • Tamiko Nishimura

    (McGill University)

  • Sidney E. Croul

    (Dalhousie University)

  • Ichiro Nakano

    (Hokuto Social Medical Corporation, Hokuto Hospital)

  • Yasser Riazalhosseini

    (McGill University)

  • Janusz Rak

    (The Research Institute of the McGill University Health Centre
    McGill University
    McGill University)

Abstract

Targeting neovascularization in glioblastoma (GBM) is hampered by poor understanding of the underlying mechanisms and unclear linkages to tumour molecular landscapes. Here we report that different molecular subtypes of human glioma stem cells (GSC) trigger distinct endothelial responses involving either angiogenic or circumferential vascular growth (vasectasia). The latter process is selectively triggered by mesenchymal (but not proneural) GSCs and is mediated by a subset of extracellular vesicles (EVs) able to transfer EGFR/EGFRvIII transcript to endothelial cells. Inhibition of the expression and phosphorylation of EGFR in endothelial cells, either pharmacologically (Dacomitinib) or genetically (gene editing), abolishes their EV responses in vitro and disrupts vasectasia in vivo. Therapeutic inhibition of EGFR markedly extends anticancer effects of VEGF blockade in mice, coupled with abrogation of vasectasia and prolonged survival. Thus, vasectasia driven by intercellular transfer of oncogenic EGFR may represent a new therapeutic target in a subset of GBMs.

Suggested Citation

  • Cristiana Spinelli & Lata Adnani & Brian Meehan & Laura Montermini & Sidong Huang & Minjun Kim & Tamiko Nishimura & Sidney E. Croul & Ichiro Nakano & Yasser Riazalhosseini & Janusz Rak, 2024. "Mesenchymal glioma stem cells trigger vasectasia—distinct neovascularization process stimulated by extracellular vesicles carrying EGFR," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46597-x
    DOI: 10.1038/s41467-024-46597-x
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