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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 Glioblastoma-Initiating Cells (GICs) challenge the design of effective therapies. We investigated GICs and non-GICs response to RT in a paired in-vitro m...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650288/ https://www.ncbi.nlm.nih.gov/pubmed/29088733 http://dx.doi.org/10.18632/oncotarget.18363 |
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author | Stanzani, Elisabetta Martínez-Soler, Fina Mateos, Teresa Martín Vidal, Noemi Villanueva, Alberto Pujana, Miquel Angel Serra-Musach, Jordi de la Iglesia, Núria Giménez-Bonafé, Pepita Tortosa, Avelina |
author_facet | Stanzani, Elisabetta Martínez-Soler, Fina Mateos, Teresa Martín Vidal, Noemi Villanueva, Alberto Pujana, Miquel Angel Serra-Musach, Jordi de la Iglesia, Núria Giménez-Bonafé, Pepita Tortosa, Avelina |
author_sort | Stanzani, Elisabetta |
collection | PubMed |
description | Glioblastoma (GBM) still remains an incurable disease being radiotherapy (RT) the mainstay treatment. Glioblastoma intra-tumoral heterogeneity and Glioblastoma-Initiating 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. |
format | Online Article Text |
id | pubmed-5650288 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-56502882017-10-30 Radioresistance of mesenchymal glioblastoma initiating cells correlates with patient outcome and is associated with activation of inflammatory program Stanzani, Elisabetta Martínez-Soler, Fina Mateos, Teresa Martín Vidal, Noemi Villanueva, Alberto Pujana, Miquel Angel Serra-Musach, Jordi de la Iglesia, Núria Giménez-Bonafé, Pepita Tortosa, Avelina Oncotarget Research Paper Glioblastoma (GBM) still remains an incurable disease being radiotherapy (RT) the mainstay treatment. Glioblastoma intra-tumoral heterogeneity and Glioblastoma-Initiating 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 Journals LLC 2017-06-03 /pmc/articles/PMC5650288/ /pubmed/29088733 http://dx.doi.org/10.18632/oncotarget.18363 Text en Copyright: © 2017 Stanzani et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Stanzani, Elisabetta Martínez-Soler, Fina Mateos, Teresa Martín Vidal, Noemi Villanueva, Alberto Pujana, Miquel Angel Serra-Musach, Jordi de la Iglesia, Núria Giménez-Bonafé, Pepita Tortosa, Avelina 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 |
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_short | 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 |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650288/ https://www.ncbi.nlm.nih.gov/pubmed/29088733 http://dx.doi.org/10.18632/oncotarget.18363 |
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