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cc-by (c) Stanzani, Elisabetta et al., 2017
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/116351

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

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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.

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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. Radioresistance of mesenchymal glioblastoma initiating cells correlates with patient outcome and is associated with activation of inflammatory program. _Oncotarget_. 2017. Vol. 8, núm. 43, pàgs. 73640-73653. [consulta: 23 de gener de 2026]. ISSN: 1949-2553. [Disponible a: https://hdl.handle.net/2445/116351]

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