Evidence map›Paper›PMID 34543427›Full record

ArticleNeuro-oncology2022

TGF-β promotes microtube formation in glioblastoma through thrombospondin 1.

Justin V Joseph, Capucine R Magaut, Simon Storevik, Luiz H Geraldo, Thomas Mathivet, Md Abdul Latif, Justine Rudewicz, Joris Guyon, Matteo Gambaretti, Frida Haukas and 23 more

Open access · bronzeAbstract read
In one paragraph

Article in Neuro-oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
6.0field-weighted citation impact, top 2% of its field
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

76 citing papers in PubMed, 105 citations in OpenAlex.

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  17. Neuro-Cancer Interactions Shape Glioma Intratumoral Heterogeneity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  18. Article
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16 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

33 authors at 13 institutions in 8 countries.

Justin V JosephDepartment of Clinical Medicine, University of Aarhus, Aarhus, Denmark.
Capucine R MagautINSERM, LAMC, U1029, University of Bordeaux, Pessac, France.
Simon StorevikDepartment of Biomedicine, University of Bergen, Bergen, Norway.
Luiz H GeraldoINSERM U970, Paris Cardiovascular Research Center, Paris, France.
Thomas MathivetINSERM U970, Paris Cardiovascular Research Center, Paris, France.
Md Abdul LatifDepartment of Biomedicine, University of Bergen, Bergen, Norway.
Justine RudewiczDepartment of Biomedicine, University of Bergen, Bergen, Norway.
Joris GuyonINSERM, LAMC, U1029, University of Bordeaux, Pessac, France.
Matteo GambarettiINSERM, LAMC, U1029, University of Bordeaux, Pessac, France.
Frida HaukasDepartment of Biomedicine, University of Bergen, Bergen, Norway.
Amalie TronesDepartment of Biomedicine, University of Bergen, Bergen, Norway.
Lars A Rømo YstaasDepartment of Biomedicine, University of Bergen, Bergen, Norway.
Jubayer A HossainDepartment of Biomedicine, University of Bergen, Bergen, Norway.
Sandra NinzimaDepartment of Biomedicine, University of Bergen, Bergen, Norway.
Sylvain CuvellierCNRS, IBGC, UMR5095, University of Bordeaux, Bordeaux, France.
Wenjing ZhouDepartment of Biomedicine, University of Bergen, Bergen, Norway.
Tushar TomarPamGene International B.V., BJ 's-Hertogenbosch, the Netherlands.
Barbara KlinkDepartment of Biomedicine, University of Bergen, Bergen, Norway.
Lalit RaneDepartment of Clinical Science, University of Bergen, Bergen, Norway.
Bronwyn K IrvingSchool of Medicine, University of Leeds, Leeds, UK.
Joanne MarrisonDepartment of Biology, University of York, York, UK.
Peter O'TooleDepartment of Biology, University of York, York, UK.
Heiko WurdakSchool of Medicine, University of Leeds, Leeds, UK.
Jian WangDepartment of Biomedicine, University of Bergen, Bergen, Norway.
Zhang DiDepartment of Neurosurgery, Qilu Hospital of Shandong University and Institute of Brain and Brain-Inspired Science, Shandong University; Shandong Key Laboratory of Brain Function Remodeling, Jinan, Shandong, P.R. China.
Even BirkelandDepartment of Biomedicine, University of Bergen, Bergen, Norway.
Frode S BervenDepartment of Biomedicine, University of Bergen, Bergen, Norway.
Frank WinklerNeurology Clinic and National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany.
Frank A E KruytDepartment of Medical Oncology, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands.
Andreas BikfalviINSERM, LAMC, U1029, University of Bordeaux, Pessac, France.
Rolf BjerkvigDepartment of Biomedicine, University of Bergen, Bergen, Norway.
Thomas DaubonDepartment of Biomedicine, University of Bergen, Bergen, Norway.
Hrvoje MileticDepartment of Biomedicine, University of Bergen, Bergen, Norway.
University of Bergen · NOUniversité de Bordeaux · FRQilu Hospital of Shandong University · CNHaukeland University Hospital · NOInserm · FRUniversity of Leeds · GBUniversity of York · GBCentre National de la Recherche Scientifique · FRLaboratoire National de Santé · LUNational Center for Tumor Diseases · DEPamGene (Netherlands) · NLParis Cardiovascular Research Center · FRUniversity Medical Center Groningen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMicrotubes (MTs), cytoplasmic extensions of glioma cells, are important cell communication structures promoting invasion and treatment resistance through network formation. MTs are abundant in chemoresistant gliomas, in particular, glioblastomas (GBMs), while they are uncommon in chemosensitive IDH-mutant and 1p/19q co-deleted oligodendrogliomas. The aim of this study was to identify potential signaling pathways involved in MT formation.

methodsBioinformatics analysis of TCGA was performed to analyze differences between GBM and oligodendroglioma. Patient-derived GBM stem cell lines were used to investigate MT formation under transforming growth factor-beta (TGF-β) stimulation and inhibition in vitro and in vivo in an orthotopic xenograft model. RNA sequencing and proteomics were performed to detect commonalities and differences between GBM cell lines stimulated with TGF-β.

resultsAnalysis of TCGA data showed that the TGF-β pathway is highly activated in GBMs compared to oligodendroglial tumors. We demonstrated that TGF-β1 stimulation of GBM cell lines promotes enhanced MT formation and communication via calcium signaling. Inhibition of the TGF-β pathway significantly reduced MT formation and its associated invasion in vitro and in vivo. Downstream of TGF-β, we identified thrombospondin 1 (TSP1) as a potential mediator of MT formation in GBM through SMAD activation. TSP1 was upregulated upon TGF-β stimulation and enhanced MT formation, which was inhibited by TSP1 shRNAs in vitro and in vivo.

conclusionTGF-β and its downstream mediator TSP1 are important mediators of the MT network in GBM and blocking this pathway could potentially help to break the complex MT-driven invasion/resistance network.

Indexed as

GlioblastomaGliomaOligodendrogliomaHumansThrombospondin 1Transforming Growth Factor betaThrombospondin 1Transforming Growth Factor betaglioblastomamicrotubesSMADTGF-βTsp1

Identifiers

PMID34543427
PMCPMC8972291
OpenAlexW3199766766

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

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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 OpenQuestion graph.