Stanzani, ElisabettaMartínez Soler, FinaMartín Mateos, TeresaVidal, NoemíVillanueva Garatachea, AlbertoPujana Genestar, M. ÁngelSerra-Musach, JordiIglesia, Núria de laGiménez Bonafé, PepitaTortosa i Moreno, Avelina2017-10-092017-10-092017-091949-2553https://hdl.handle.net/2445/116351Glioblastoma (GBM) still remains an incurable disease being radiotherapy (RT) the mainstay treatment. Glioblastoma intra-tumoral heterogeneity and GlioblastomaInitiating Cells (GICs) challenge the design of effective therapies. We investigated GICs and non-GICs response to RT in a paired in-vitro model and addressed molecular programs activated in GICs after RT. Established GICs heterogeneously expressed several GICs markers and displayed a mesenchymal signature. Upon fractionated RT, GICs reported higher radioresistance compared to non-GICs and showed lower α- and β-values, according to the Linear Quadratic Model interpretation of the survival curves. Moreover, a significant correlation was observed between GICs radiosensitivity and patient disease-free survival. Transcriptome analysis of GICs after acquisition of a radioresistant phenotype reported significant activation of Proneural-to-Mesenchymal transition (PMT) and pro-inflammatory pathways, being STAT3 and IL6 the major players. Our findings support a leading role of mesenchymal GICs in defining patient response to RT and provide the grounds for targeted therapies based on the blockade of inflammatory pathways to overcome GBM radioresistance.14 p.application/pdfengcc-by (c) Stanzani, Elisabetta et al., 2017http://creativecommons.org/licenses/by/3.0/esGliomaTumors cerebralsCèl·lules mareResistència als medicamentsRadioteràpiaGliomasBrain tumorsStem cellsDrug resistanceRadiotherapyinfo:eu-repo/semantics/article6713782017-10-09info:eu-repo/semantics/openAccess29088733