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dc.creatorAbou-Faycal, C. (Cherine)-
dc.creatorBrambilla, E. (E.)-
dc.creatorAgorreta, J. (Jackeline)-
dc.creatorLepeltier, N. (Nina)-
dc.creatorJacquet, T. (Thibault)-
dc.creatorLemaitre, N. (Nicolas)-
dc.creatorEmadali, A. (Anouk)-
dc.creatorLucas, A. (Anthony)-
dc.creatorLacal, P.M. (Pedro M.)-
dc.creatorMontuenga-Badia, L.M. (Luis M.)-
dc.creatorPio, R. (Rubén)-
dc.creatorGazzeri, S. (Sylvie)-
dc.creatorEymin, B. (Beatrice)-
dc.identifier.citationAbou-Faycal, C. (Cherine); Brambilla, E. (E.); Agorreta, J. (Jackeline); et al. "The sVEGFR1-i13 splice variant regulates a beta 1 integrin/VEGFR autocrine loop involved in the progression and the response to anti-angiogenic therapies of squamous cell lung carcinoma". British journal of cancer. 118 (12), 2018, 1596 - 1608es
dc.description.abstractBACKGROUND: While lung adenocarcinoma patients can somewhat benefit from anti-angiogenic therapies, patients with squamous cell lung carcinoma (SQLC) cannot. The reasons for this discrepancy remain largely unknown. Soluble VEGF receptor-1, namely sVEGFR1-i13, is a truncated splice variant of the cell membrane-spanning VEGFR1 that has no transmembrane or tyrosine kinase domain. sVEGFR1-i13 is mainly viewed as an anti-angiogenic factor which counteracts VEGF-A/VEGFR signalling in endothelial cells. However, its role in tumour cells is poorly known. METHODS: mRNA and protein status were analysed by Real-Time qPCR, western blotting, ELISA assay, proximity ligation assay or immunohistochemistry in human tumour cell lines, murine tumourgrafts and non small cell lung carcinoma patients samples. RESULTS: We show that anti-angiogenic therapies specifically increase the levels of sVEGFR1-i13 in SQLC cell lines and chemically induced SQLC murine tumourgrafts. At the molecular level, we characterise a sVEGFR1-i13/β1 integrin/VEGFR autocrine loop which determines whether SQLC cells proliferate or go into apoptosis, in response to anti-angiogenic therapies. Furthermore, we show that high levels of both sVEGFR1-i13 and β1 integrin mRNAs and proteins are associated with advanced stages in SQLC patients and with a poor clinical outcome in patients with early stage SQLC. CONCLUSIONS: Overall, these results reveal an unexpected pro-tumoural function of sVEGFR1-i13 in SQLC tumour cells, which contributes to their progression and escape from anti-angiogenic therapies. These data might help to understand why some SQLC patients do not respond to anti-angiogenic therapies.es_ES
dc.description.sponsorshipThis work was supported by Institut National de la Recherche (INSERM), by Centre National de la Recherche Scientifique (CNRS), by University Grenoble Alpes, by the Comité Départemental Isère de la Ligue Nationale contre le Cancer, by the INCa/ DHOS (Appel d’Offre Recherche Translationnelle), by the Fondation de France (Projet Grande Ampleur), by ROCHE fellowship (Bourse de Recherche Fondamentale), by the Fondation ARC pour la Recherche Contre le Cancer and by Fonds de dotation AGIR pour les Maladies Chroniques. Cherine Abou Faycal was supported by the Ligue Nationale Contre Le Cancer.es_ES
dc.publisherSpringer Sciencees_ES
dc.subjectSquamous cell lung carcinoma (SQLC)es_ES
dc.subjectAnti-angiogenic therapieses_ES
dc.titleThe sVEGFR1-i13 splice variant regulates a beta 1 integrin/VEGFR autocrine loop involved in the progression and the response to anti-angiogenic therapies of squamous cell lung carcinomaes_ES
dc.description.noteThis work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).es_ES
dadun.citation.publicationNameBritish journal of canceres_ES

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