ArticleEBioMedicine2019
A GBM-like V-ATPase signature directs cell-cell tumor signaling and reprogramming via large oncosomes.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 43 citations in OpenAlex.
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- Large extracellular vesicles and blebbisomes in cancer: emerging and translational opportunities highlights.Cell communication and signaling : CCS · 2026Review
- Analysis of BAL extracellular vesicles unveils NF-κB activation at the onset of chronic lung allograft dysfunction.Clinical science (London, England : 1979) · 2026Article
- Network-Based Prediction of Oligodendroglioma Driver Gene Candidates within the Region of the 1p/19q Co-deletion Utilizing Single-Cell Transcriptomes.Computational and structural biotechnology journal · 2026Article
- Utilizing Extracellular Vesicles for Delivering Therapies in Neurodegenerative Disorders.Current drug delivery · 2026Review
- Article
- Proteomic profiling reveals dynamic regulation of vesicle trafficking across glioma grades.Journal of neuro-oncology · 2025Article
- Extracellular vesicle heterogeneity through the lens of multiomics.Cell reports. Medicine · 2025Article
- Blebbisomes are large, organelle-rich extracellular vesicles with cell-like properties.Nature cell biology · 2025Article
- V-ATPase in glioma stem cells: a novel metabolic vulnerability.Journal of experimental & clinical cancer research : CR · 2025Article
- Proteomics Studies on Extracellular Vesicles Derived from Glioblastoma: Where Do We Stand?International journal of molecular sciences · 2024Review
- Yin-Yang: two sides of extracellular vesicles in inflammatory diseases.Journal of nanobiotechnology · 2024Review
- Extracellular Vesicles as Drug Delivery System for Cancer Therapy.Pharmaceutics · 2024Review
- Vacuolar Proton-Translocating ATPase May Take Part in the Drug Resistance Phenotype of Glioma Stem Cells.International journal of molecular sciences · 2024Article
- Decoding the secret of extracellular vesicles in the immune tumor microenvironment of the glioblastoma: on the border of kingdoms.Frontiers in immunology · 2024Review
- Crosstalk Between Macrophages and Breast Cancer Cells: Networking Within Tumors.Results and problems in cell differentiation · 2024Review
- Identification and validation of ATP6V1G1-regulated phosphorylated proteins in hepatocellular carcinoma.PloS one · 2024Article
- Extracellular vesicles and nanoparticles: emerging complexities.Trends in cell biology · 2023Review
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe V-ATPase proton pump controls acidification of intra and extra-cellular milieu in both physiological and pathological conditions. We previously showed that some V-ATPase subunits are enriched in glioma stem cells and in patients with poor survival. In this study, we investigated how expression of a GBM-like V-ATPase pump influences the non-neoplastic brain microenvironment.
methodsLarge oncosome (LO) vesicles were isolated from primary glioblastoma (GBM) neurospheres, or from patient sera, and co-cultured with primary neoplastic or non-neoplastic brain cells. LO transcript and protein contents were analyzed by qPCR, immunoblotting and immunogold staining. Activation of pathways in recipient cells was determined at gene and protein expression levels. V-ATPase activity was impaired by Bafilomycin A1 or gene silencing.
findingsGBM neurospheres influence their non-neoplastic microenvironment by delivering the V-ATPase subunit V1G1 and the homeobox genes HOXA7, HOXA10, and POU3F2 to recipient cells via LO. LOs reprogram recipient cells to proliferate, grow as spheres and to migrate. Moreover, LOs are particularly abundant in the circulation of GBM patients with short survival time. Finally, impairment of V-ATPase reduces LOs activity.
interpretationWe identified a novel mechanism adopted by glioma stem cells to promote disease progression via LO-mediated reprogramming of their microenvironment. Our data provide preliminary evidence for future development of LO-based liquid biopsies and suggest a novel potential strategy to contrast glioma progression. FUND: This work was supported by Fondazione Cariplo (2014-1148 to VV) and by the Italian Minister of Health-Ricerca Corrente program 2017 (to SF).
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