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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 |
Keywords: | Glioma Tumors cerebrals Cèl·lules mare Resistència als medicaments Radioteràpia Gliomas Brain tumors Stem cells Drug resistance Radiotherapy |
Issue Date: | Sep-2017 |
Publisher: | Impact Journals |
Abstract: | 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.18632/oncotarget.18363 |
It is part of: | Oncotarget, 2017, vol. 8, num. 43, p. 73640-73653 |
URI: | http://hdl.handle.net/2445/116351 |
Related resource: | https://doi.org/10.18632/oncotarget.18363 |
ISSN: | 1949-2553 |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Infermeria Fonamental i Clínica) |
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