To access the full text documents, please follow this link: http://hdl.handle.net/2445/116351

Title:	Radioresistance of mesenchymal glioblastoma initiating cells correlates with patient outcome and is associated with activation of inflammatory program
Author:	Stanzani, Elisabetta; Martínez Soler, Fina; Martín Mateos, Teresa; Vidal, Noemí; Villanueva Garatachea, Alberto; Pujana Genestar, M. Ángel; Serra-Musach, Jordi; Iglesia, Núria de la; Giménez Bonafé, Pepita; Tortosa i Moreno, Avelina
Notes:	Glioblastoma (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.
Subject(s):	-Glioma -Tumors cerebrals -Cèl·lules mare -Resistència als medicaments -Radioteràpia -Gliomas -Brain tumors -Stem cells -Drug resistance -Radiotherapy
Rights:	cc-by (c) Stanzani, Elisabetta et al., 2017 http://creativecommons.org/licenses/by/3.0/es
Document type:	Article Article - Published version
Published by:	Impact Journals
Share:

Show full item record