Evidence map›Paper›PMID 39883079›Full record

ArticleNeuro-oncology2025

Extracellular vesicles released by glioblastoma cancer cells drive tumor invasiveness via Connexin-43 gap junctions.

Matteo Tamborini, Valentino Ribecco, Elisabetta Stanzani, Arianna Sironi, Monica Tambalo, Davide Franzone, Elena Florio, Edoardo Fraviga, Chiara Saulle, Maria C Gagliani and 12 more

Abstract read
In one paragraph

Article in Neuro-oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Organoids glimpse: the nexus for diverse tumor heterogeneity.Frontiers in cell and developmental biology · 2026
    Review
  7. Review
  8. Article
  9. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors.

Matteo TamboriniCNR Institute of Neuroscience c/o IRCCS Humanitas Research Hospital, Rozzano, Milano, 20089, Italy.ORCID 0000-0002-2236-2956
Valentino RibeccoIRCCS Humanitas Research Hospital, Rozzano, Milano, 20089, Italy.
Elisabetta StanzaniDepartment of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milano, 20072, Italy.
Arianna SironiDepartment of Experimental Medicine (DIMES), Cellular Electron Microscopy Laboratory, Università di Genova, Genova, 16132, Italy.
Monica TambaloDepartment of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milano, 20072, Italy.
Davide FranzoneDepartment of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milano, 20072, Italy.
Elena FlorioDepartment of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milano, 20072, Italy.
Edoardo FravigaDepartment of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milano, 20072, Italy.
Chiara SaulleDepartment of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milano, 20072, Italy.
Maria C GaglianiDepartment of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA.
Marco PizzocriIRCCS Humanitas Research Hospital, Rozzano, Milano, 20089, Italy.
Milena MattioliDepartment of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milano, 20072, Italy.
Katia CorteseDepartment of Experimental Medicine (DIMES), Cellular Electron Microscopy Laboratory, Università di Genova, Genova, 16132, Italy.
Jean X JiangDepartment of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA.
Giuseppe MartanoIRCCS Humanitas Research Hospital, Rozzano, Milano, 20089, Italy.
Letterio S PolitiDepartment of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milano, 20072, Italy.
Marco RivaDepartment of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milano, 20072, Italy.
Federico PessinaDepartment of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milano, 20072, Italy.ORCID 0000-0002-8717-4999
Davide PozziDepartment of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milano, 20072, Italy.
Simona LodatoDepartment of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milano, 20072, Italy.
Lorena PassoniIRCCS Humanitas Research Hospital, Rozzano, Milano, 20089, Italy.
Michela MatteoliDepartment of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milano, 20072, Italy.

Funding

AIRC fellowship for Italy 22546AIRC per la Ricerca sul Cancro IG 18851AIRC per la Ricerca sul Cancro IG 24905Fondazione Umberto VeronesiFRRB grant NEVERMIND CP2_16/2018Ministero dell'Università e della Ricerca PRIN2020PBS5MJNational Plan for Complementary Investments CUP B53C22006100001Welch Foundation AQ-1507
6 · The paper itself

Abstract

backgroundAlthough invasiveness is one of the major determinants of the poor glioblastoma (GBM) outcome, the mechanisms of GBM invasion are only partially understood. Among the intrinsic and environmental processes promoting cell-to-cell interaction processes, eventually driving GBM invasion, we focused on the pro-invasive role played by extracellular vesicles (EVs), a heterogeneous group of cell-released membranous structures containing various bioactive cargoes, which can be transferred from donor to recipient cells.

methodsExtracellular vesicles isolated from patient-derived GBM cell lines and surgical aspirates were assessed for their pro-migratory competence by spheroid migration assays, calcium imaging, and PYK2/FAK phosphorylation. Brain invasiveness was investigated in human cortical organoids-based assembloids and in vivo orthotopic xenografts. Extracellular vesicles' molecular features were specified by multiplex bead-based flow cytometry.

resultsResults unveil a self-sustaining mechanism triggering migration through autocrine release and engagement of a specific population of EVs of large size (L-EVs), isolated from either patient-derived cell lines or surgical aspirates. Large size-EVs act through modulation of calcium transients via Connexin 43-Gap Junctions (Cx43-GJ) and phospho-activation of PYK2. Preincubation with blocking antibodies targeting Cx43 hemichannels demonstrated a dose-dependent inhibition of the L-EV-mediated GBM migration. By exploiting patients' surgical aspirates, we show that only L-EVs deriving from tumoral cells, and not those with immune origin, promote tumor migration, impacting more prominently the tumoral cells with mesenchymal subtype.

conclusionsWe demonstrate that L-EVs released by GBM cells, but not by the immune cells of the tumor microenvironment, represent a relevant and unique autocrine pro-migratory input for the tumor.

Indexed as

Brain NeoplasmsConnexin 43Extracellular VesiclesGap JunctionsGlioblastomaAnimalsCell Line, TumorCell MovementFocal Adhesion Kinase 2HumansMiceNeoplasm InvasivenessTumor Cells, CulturedConnexin 43Focal Adhesion Kinase 2GJA1 protein, humanassembloidscalcium signalingConnexin-43extracellular vesiclesfocal adhesion complexglioblastomainvasionmigrationstem cellssurgical aspirate

Identifiers

PMID39883079
PMCPMC12908494

What Socratic holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.