Article (Scientific journals)
CXCL12 mediates glioblastoma resistance to radiotherapy in the subventricular zone.
Goffart, Nicolas; LOMBARD, Arnaud; Lallemand, François et al.
2017In Neuro-Oncology, 19 (1), p. 66-77
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Keywords :
CXCL12; glioblastoma; mesenchymal activation; radioresistance; subventricular zone
Abstract :
[en] BACKGROUND: Patients with glioblastoma (GBM) have an overall median survival of 15 months despite multimodal therapy. These catastrophic survival rates are to be correlated to systematic relapses that might arise from remaining glioblastoma stem cells (GSCs) left behind after surgery. In this line, it has recently been demonstrated that GSCs are able to escape the tumor mass and preferentially colonize the adult subventricular zone (SVZ). At a distance from the initial tumor site, these GSCs might therefore represent a high-quality model of clinical resilience to therapy and cancer relapses as they specifically retain tumor-initiating abilities. METHOD: While relying on recent findings that have validated the existence of GSCs in the human SVZ, we questioned the role of the SVZ niche as a potential GSC reservoir involved in therapeutic failure. RESULTS: Our results demonstrate that (i) GSCs located in the SVZ are specifically resistant to radiation in vivo, (ii) these cells display enhanced mesenchymal roots that are known to be associated with cancer radioresistance, (iii) these mesenchymal traits are specifically upregulated by CXCL12 (stromal cell-derived factor-1) both in vitro and in the SVZ environment, (iv) the amount of SVZ-released CXCL12 mediates GBM resistance to radiation in vitro, and (v) interferes with the CXCL12/CXCR4 signalling system, allowing weakening of the tumor mesenchymal roots and radiosensitizing SVZ-nested GBM cells. CONCLUSION: Together, these data provide evidence on how the adult SVZ environment, through the release of CXCL12, supports GBM therapeutic failure and potential tumor relapse.
Research center :
Giga-Neurosciences - ULiège
Disciplines :
Oncology
Genetics & genetic processes
Author, co-author :
Goffart, Nicolas  ;  Université de Liège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, et biochimie humaine
LOMBARD, Arnaud   ;  Centre Hospitalier Universitaire de Liège - CHU > Service de neurochirurgie
Lallemand, François  ;  Université de Liège > Département des sciences cliniques > Radiothérapie
Kroonen, Jerome
Nassen, Jessica 
Di Valentin, Emmanuel  ;  Université de Liège > Département des sciences de la vie > GIGA-R : Virologie et immunologie
Berendsen, Sharon
Dedobbeleer, Matthias ;  Université de Liège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, et biochimie humaine
Willems, Estelle ;  Université de Liège - ULiège > Doct. sc. bioméd. & pharma. (paysage)
Robe, Pierre ;  Université de Liège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Bours, Vincent ;  Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Génétique humaine
Martin, Didier  ;  Université de Liège > Département des sciences cliniques > Neurochirurgie
Martinive, Philippe ;  Université de Liège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Maquet, Pierre  ;  Université de Liège > Département des sciences cliniques > Neurologie
Rogister, Bernard  ;  Université de Liège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, et biochimie humaine
More authors (5 more) Less
 These authors have contributed equally to this work.
Language :
English
Title :
CXCL12 mediates glioblastoma resistance to radiotherapy in the subventricular zone.
Publication date :
2017
Journal title :
Neuro-Oncology
ISSN :
1522-8517
eISSN :
1523-5866
Publisher :
Oxford University Press
Volume :
19
Issue :
1
Pages :
66-77
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
Etude des mécanismes de rechute du Glioblastome
Commentary :
(c) The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Available on ORBi :
since 30 January 2017

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