Radioresistance of mesenchymal glioblastoma initiating cells correlates with patient outcome and is associated with activation of inflammatory program
| Autor: | 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 |
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| Přispěvatelé: | Universitat de Barcelona |
| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona Recercat. Dipósit de la Recerca de Catalunya instname |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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