ArticleCancer cell international2024
Extracellular vesicles produced by irradiated endothelial or Glioblastoma stem cells promote tumor growth and vascularization modulating tumor microenvironment.
Article in Cancer cell international, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 29 citations in OpenAlex.
- Extracellular Vesicles in Diffuse Midline Glioma: Emerging Mediators of Radiation Response and Therapeutic Resistance.Cancers · 2026Review
- Review
- Single-cell landscape of melanoma reveals ETV5-driven C3 ID4Frontiers in immunology · 2026Article
- Progress in the study of molecular markers in the prognosis assessment and recurrence patterns of glioblastoma.Cancer biology & therapy · 2025Review
- DUSP8 as a regulator of glioblastoma stem-like cell contribution to tumor vascularization.Journal of experimental & clinical cancer research : CR · 2025Article
- TurboID-Mediated Profiling of Glioblastoma-Derived Extracellular Vesicle Cargo Proteins.Journal of extracellular vesicles · 2025Article
- Irradiation of prostate cancer alters circulating small extracellular vesicle functions.Scientific reports · 2025Article
- In Vitro Analysis of PMEPA1 Upregulation in Mesenchymal Stem Cells Induced by Prostate Cancer Cells.International journal of molecular sciences · 2025Article
- The Role of Senescence, its Therapeutic Relevance and Clinical Implications in the Tumor Microenvironment.Theranostics · 2025Review
- The dual role of POSTN in maintaining glioblastoma stem cells and the immunosuppressive phenotype of microglia in glioblastoma.Journal of experimental & clinical cancer research : CR · 2024Article
- Hsp70 and Calcitonin Receptor Protein in Extracellular Vesicles from Glioblastoma Multiforme: Biomarkers with Putative Roles in Carcinogenesis and Potential for Differentiating Tumor Types.International journal of molecular sciences · 2024Article
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15 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundGlioblastoma (GBM) is the most lethal primary brain tumor in adult, characterized by highly aggressive and infiltrative growth. The current therapeutic management of GBM includes surgical resection followed by ionizing radiations and chemotherapy. Complex and dynamic interplay between tumor cells and tumor microenvironment drives the progression and contributes to therapeutic resistance. Extracellular vesicles (EVs) play a crucial role in the intercellular communication by delivering bioactive molecules in the surrounding milieu modulating tumor microenvironment.
methodsIn this study, we isolated by ultracentrifugation EVs from GBM stem-like cell (GSC) lines and human microvascular endothelial cells (HMVECs) exposed or not to ionizing irradiation. After counting and characterization, we evaluated the effects of exposure of GSCs to EVs isolated from endothelial cells and vice versa. The RNA content of EVs isolated from GSC lines and HMVECs exposed or not to ionizing irradiation, was analyzed by RNA-Seq. Periostin (POSTN) and Filamin-B (FLNB) emerged in gene set enrichment analysis as the most interesting transcripts enriched after irradiation in endothelial cell-derived EVs and GSC-derived EVs, respectively. POSTN and FLNB expression was modulated and the effects were analyzed by in vitro assays.
resultsWe confirmed that ionizing radiations increased EV secretion by GSCs and normal endothelial cells, affected the contents of and response to cellular secreted EVs. Particularly, GSC-derived EVs decreased radiation-induced senescence and promoted migration in HMVECs whereas, endothelial cell-derived EVs promoted tumorigenic properties and endothelial differentiation of GSCs. RNA-Seq analysis of EV content, identified FLNB and POSTN as transcripts enriched in EVs isolated after irradiation from GSCs and HMVECs, respectively. Assays performed on POSTN overexpressing GSCs confirmed the ability of POSTN to mimic the effects of endothelial cell-derived EVs on GSC migration and clonogenic abilities and transdifferentiation potential. Functional assays performed on HMVECs after silencing of FLNB supported its role as mediator of the effects of GSC-derived EVs on senescence and migration.
conclusionIn this study, we identified POSTN and FLNB as potential mediators of the effects of EVs on GSC and HMVEC behavior confirming that EVs play a crucial role in the intercellular communication by delivering bioactive molecules in the surrounding milieu modulating tumor microenvironment.
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