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

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
DOI: 10.1038/s41467-024-46597-x Publication Date: 2024-04-03T09:02:54Z
ABSTRACT
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.
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