Oligodendroglioma cells modulate tumour growth via extracellular vesicle biogenesis

ABSTRACT: Oligodendroglioma driver mutations are known, yet signature slow growth rates of these glial tumours are poorly understood. Here we show using patient biopsies that neoplastic and non-neoplastic cells in the tumour mass display elevated ERK signaling, proliferate ectopically, and undergo cell death. Oligodendroglioma cell cross-talk with the tumour microenvironment is mediated partly by extracellular vesicles, which inhibit astrocyte expansion in vitro. Elevated extracellular vesicle biogenesis gene (SMPD3,TSG101) expression positively correlates with longer patient survival. Accordingly, SMPD3 and TSG101 knock-down enhances oligodendroglioma cell expansion whereas overexpression slows cell growth. SMPD3 knock-down also enhances oligodendroglioma growth in cortical xenografts and in human cerebral organoids. Shared signature features of ODG cell line-derived vesicular proteomes include ribosomal biogenesis proteins, whereas the soluble secretome is growth factor-rich, the pro-proliferative effects of which are blocked by foretinib. Oligodendroglioma cell growth is thus controlled by the combined effects of cytostatic/cytotoxic extracellular vesicles and soluble pro-proliferative growth factors.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Oligodendrocyte, Cell Culture

DISEASE(S): Oligodendroglioma

SUBMITTER: Thomas Olender  

LAB HEAD: Carol Schuurmans

PROVIDER: PXD078419 | Pride | 2026-07-01

REPOSITORIES: Pride