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dc.contributor.authorDaubon, Thomasen_US
dc.contributor.authorLéon, Célineen_US
dc.contributor.authorClarke, Kimen_US
dc.contributor.authorAndrique, Laetitiaen_US
dc.contributor.authorSalabert, Lauraen_US
dc.contributor.authorDarbo, Elodieen_US
dc.contributor.authorPineau, Raphaelen_US
dc.contributor.authorGuérit, Sylvaineen_US
dc.contributor.authorMaitre, Marlèneen_US
dc.contributor.authorDedieu, Stéphaneen_US
dc.contributor.authorJeanne, Albinen_US
dc.contributor.authorBailly, Sabineen_US
dc.contributor.authorFeige, Jean-Jacquesen_US
dc.contributor.authorMiletic, Hrvojeen_US
dc.contributor.authorRossi, Marcoen_US
dc.contributor.authorBello, Lorenzoen_US
dc.contributor.authorFalciani, Francescoen_US
dc.contributor.authorBjerkvig, Rolfen_US
dc.contributor.authorBikfalvi, Andréasen_US
dc.PublishedDaubon T, Léon, Clarke K, Andrique, Salabert, Darbo, Pineau, Guérit, Maitre, Dedieu, Jeanne, Bailly, Feige, Miletic H, Rossi M, Bello L, Falciani F, Bjerkvig R, Bikfalvi. Deciphering the complex role of thrombospondin-1 in glioblastoma development. Nature Communications. 2019;10:1146eng
dc.description.abstractWe undertook a systematic study focused on the matricellular protein Thrombospondin-1 (THBS1) to uncover molecular mechanisms underlying the role of THBS1 in glioblastoma (GBM) development. THBS1 was found to be increased with glioma grades. Mechanistically, we show that the TGFβ canonical pathway transcriptionally regulates THBS1, through SMAD3 binding to the THBS1 gene promoter. THBS1 silencing inhibits tumour cell invasion and growth, alone and in combination with anti-angiogenic therapy. Specific inhibition of the THBS1/CD47 interaction using an antagonist peptide decreases cell invasion. This is confirmed by CD47 knock-down experiments. RNA sequencing of patient-derived xenograft tissue from laser capture micro-dissected peripheral and central tumour areas demonstrates that THBS1 is one of the gene with the highest connectivity at the tumour borders. All in all, these data show that TGFβ1 induces THBS1 expression via Smad3 which contributes to the invasive behaviour during GBM expansion. Furthermore, tumour cell-bound CD47 is implicated in this process.en_US
dc.publisherSpringer Natureeng
dc.rightsAttribution CC BYeng
dc.titleDeciphering the complex role of thrombospondin-1 in glioblastoma developmenten_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2019 The Authors
dc.source.journalNature Communications

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