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

• DOI: 10.1038/s41467-024-46597-x
• Publication Date: 2024-04-03T09:02:54Z
• Authors: Cristiana Spinelli; Lata Adnani; Brian Meehan; Laura Montermini; Sidong Huang; Minjun Kim; Tamiko Nishimura; Sidney E. Croul; Ichiro Nakano; Yasser Riazalhoss...; Janusz Rak
• Keywords: 0303 health sciences; Brain Neoplasms; Science; Q; Endothelial Cells; Glioma; Article; ErbB Receptors; Mice; Extracellular Vesicles; 03 medical and health sciences; Neoplastic Stem Cells; Humans; Animals; Glioblastoma

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 subtypes human glioma stem cells (GSC) trigger distinct endothelial responses involving either angiogenic or circumferential vascular growth (vasectasia). The latter process selectively triggered mesenchymal (but not proneural) GSCs mediated a subset extracellular vesicles (EVs) able transfer EGFR/EGFRvIII transcript cells. Inhibition expression phosphorylation EGFR cells, pharmacologically (Dacomitinib) genetically (gene editing), abolishes their EV vitro disrupts vasectasia vivo. Therapeutic inhibition markedly extends anticancer effects VEGF blockade mice, coupled with abrogation prolonged survival. Thus, driven intercellular oncogenic may represent new therapeutic target GBMs.