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dc.contributor.authorRackov, Gorjana
dc.contributor.authorIegiani, Giorgia
dc.contributor.authorUribe, Daniel
dc.contributor.authorQuezada, Claudia
dc.contributor.authorBelda-Iniesta, Cristobal 
dc.contributor.authorEscobedo-Lucea, Carmen
dc.contributor.authorSilva, Augusto
dc.contributor.authorPuig, Pere
dc.contributor.authorGonzález-Rumayor, Víctor
dc.contributor.authorAyuso-Sacido, Ángel
dc.date.accessioned2020-10-07T16:02:05Z
dc.date.available2020-10-07T16:02:05Z
dc.date.issued2020-08-14
dc.identifier.citationFrontiers in Oncology. 2020;10:1665es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/11103
dc.description.abstractGlioblastoma (GBM) is the most devastating and least treatable brain tumor with median survival <15 months and extremely high recurrence rates. Promising results of immune checkpoint blockade obtained from pre-clinical studies in mice did not translate to clinic, and new strategies are urgently needed, particularly those targeting GBM stem cells (GSCs) that are held responsible for drug resistance and tumor recurrence. Patient-derived GSC cultures are critical for finding effective brain tumor therapies. Here, we investigated the ability of the recently described monoclonal antibody Nilo1 to specifically recognize GSCs isolated from GBM surgical samples. We employed five patient-derived GSC cultures with different stemness marker expression and differentiation potential, able to recapitulate original tumors when xenotransplanted in vivo. To answer whether Nilo1 has any functional effects in patient-derived GSCs lines, we treated the cells with Nilo1 in vitro and analyzed cell proliferation, cell cycle, apoptosis, sphere formation, as well as the expression of stem vs. differentiation markers. All tested GSCs stained positively for Nilo1, and the ability of Nilo1 to recognize GSCs strongly relied on their stem-like phenotype. Our results showed that a subset of patient-derived GSCs were sensitive to Nilo1 treatment. In three GSC lines Nilo1 triggered differentiation accompanied by the induction of p21. Most strikingly, in one GSC line Nilo1 completely abrogated self-renewal and led to Bax-associated apoptosis. Our data suggest that Nilo1 targets a molecule functionally relevant for stemness maintenance and pinpoint Nilo1 as a novel antibody-based therapeutical strategy to be used either alone or in combination with cytotoxic drugs for GSC targeting. Further pre-clinical studies are needed to validate the effectiveness of GSC-specific Nilo1 targeting in vivo.es_ES
dc.description.sponsorshipThis work was funded by the Spanish Ministry of Economy, Industry and Competitivity (RTC-2015-3846-1) grant to ÁA-S and VG-R, “Fondo de Investigaciones Sanitarias” (FIS) (PI17-01489), and the Miguel Servet program (CP11/00147 and CPII16/00056) from the Instituto de Salud Carlos III to ÁA-S. GR holds postdoctoral Juan de la Cierva Fellowship. GI was funded by Erasmus program. DU holds Doctorado Nacional CONICYT fellowship. CQ was funded by FONDECYT (N° 1160777).es_ES
dc.language.isoenges_ES
dc.publisherFrontierses_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectNilo1es_ES
dc.subjectAntibodyes_ES
dc.subjectGlioblastomaes_ES
dc.subjectGlioma stem cellses_ES
dc.subjectImmunotherapyes_ES
dc.subjectNeural stem cells.es_ES
dc.titlePotential Therapeutic Effects of the Neural Stem Cell-Targeting Antibody Nilo1 in Patient-Derived Glioblastoma Stem Cellses_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID32974206es_ES
dc.format.volume10es_ES
dc.identifier.doi10.3389/fonc.2020.01665es_ES
dc.contributor.funderMinisterio de Economía, Industria y Competitividad (España)
dc.contributor.funderInstituto de Salud Carlos III 
dc.description.peerreviewedes_ES
dc.identifier.e-issn2234-943Xes_ES
dc.relation.publisherversionhttps://www.frontiersin.org/article/10.3389/fonc.2020.01665es_ES
dc.identifier.journalFrontiers in Oncologyes_ES
dc.repisalud.centroISCIII::Servicios Centrales::Subdirección General de Evaluación y Fomento de la Investigaciónes_ES
dc.repisalud.institucionISCIIIes_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/RTC-2015-3846-1es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/PI17-01489es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/CP11/00147es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/CPII16/00056es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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