Radioresistance of mesenchymal glioblastoma initiating cells correlates with patient outcome and is associated with activation of inflammatory program

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 mo...

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Autores: 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/116351
Acceso en línea:https://hdl.handle.net/2445/116351
Access Level:acceso abierto
Palabra clave:Glioma
Tumors cerebrals
Cèl·lules mare
Resistència als medicaments
Radioteràpia
Gliomas
Brain tumors
Stem cells
Drug resistance
Radiotherapy
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spelling Radioresistance of mesenchymal glioblastoma initiating cells correlates with patient outcome and is associated with activation of inflammatory programStanzani, ElisabettaMartínez Soler, FinaMartín Mateos, TeresaVidal, NoemíVillanueva Garatachea, AlbertoPujana Genestar, M. ÁngelSerra-Musach, JordiIglesia, Núria de laGiménez Bonafé, PepitaTortosa i Moreno, AvelinaGliomaTumors cerebralsCèl·lules mareResistència als medicamentsRadioteràpiaGliomasBrain tumorsStem cellsDrug resistanceRadiotherapyGlioblastoma (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.Impact Journals2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/116351Articles publicats en revistes (Ciències Fisiològiques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.18632/oncotarget.18363Oncotarget, 2017, vol. 8, num. 43, p. 73640-73653https://doi.org/10.18632/oncotarget.18363cc-by (c) Stanzani, Elisabetta et al., 2017http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1163512026-05-27T06:46:51Z
dc.title.none.fl_str_mv Radioresistance of mesenchymal glioblastoma initiating cells correlates with patient outcome and is associated with activation of inflammatory program
title Radioresistance of mesenchymal glioblastoma initiating cells correlates with patient outcome and is associated with activation of inflammatory program
spellingShingle Radioresistance of mesenchymal glioblastoma initiating cells correlates with patient outcome and is associated with activation of inflammatory program
Stanzani, Elisabetta
Glioma
Tumors cerebrals
Cèl·lules mare
Resistència als medicaments
Radioteràpia
Gliomas
Brain tumors
Stem cells
Drug resistance
Radiotherapy
title_short Radioresistance of mesenchymal glioblastoma initiating cells correlates with patient outcome and is associated with activation of inflammatory program
title_full Radioresistance of mesenchymal glioblastoma initiating cells correlates with patient outcome and is associated with activation of inflammatory program
title_fullStr Radioresistance of mesenchymal glioblastoma initiating cells correlates with patient outcome and is associated with activation of inflammatory program
title_full_unstemmed Radioresistance of mesenchymal glioblastoma initiating cells correlates with patient outcome and is associated with activation of inflammatory program
title_sort Radioresistance of mesenchymal glioblastoma initiating cells correlates with patient outcome and is associated with activation of inflammatory program
dc.creator.none.fl_str_mv 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
author Stanzani, Elisabetta
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Glioma
Tumors cerebrals
Cèl·lules mare
Resistència als medicaments
Radioteràpia
Gliomas
Brain tumors
Stem cells
Drug resistance
Radiotherapy
topic Glioma
Tumors cerebrals
Cèl·lules mare
Resistència als medicaments
Radioteràpia
Gliomas
Brain tumors
Stem cells
Drug resistance
Radiotherapy
description 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.
publishDate 2017
dc.date.none.fl_str_mv 2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/116351
url https://hdl.handle.net/2445/116351
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.18632/oncotarget.18363
Oncotarget, 2017, vol. 8, num. 43, p. 73640-73653
https://doi.org/10.18632/oncotarget.18363
dc.rights.none.fl_str_mv cc-by (c) Stanzani, Elisabetta et al., 2017
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Stanzani, Elisabetta et al., 2017
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Impact Journals
publisher.none.fl_str_mv Impact Journals
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300719

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