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Author (up) Goffart, N.; Lombard, A.; Lallemand, F.; Kroonen, J.; Nassen, J.; Di Valentin, E.; Berendsen, S.; Dedobbeleer, M.; Willems, E.; Robe, P.; Bours, V.; Martin, D.; Martinive, P.; Maquet, P.; Rogister, B. url  doi
  Title CXCL12 mediates glioblastoma resistance to radiotherapy in the subventricular zone Type Journal Article
  Year 2017 Publication Neuro-Oncology Abbreviated Journal Neuro Oncol  
  Volume 19 Issue 1 Pages 66-77  
  Keywords Animals; Brain Neoplasms/metabolism/*pathology/radiotherapy; Chemokine CXCL12/*metabolism; Cranial Irradiation/*adverse effects; Gamma Rays/adverse effects; Glioblastoma/metabolism/*pathology/radiotherapy; Humans; Lateral Ventricles/metabolism/*pathology/radiation effects; Mice; Mice, Nude; Neoplastic Stem Cells/metabolism/*pathology/radiation effects; *Radiation Tolerance; Signal Transduction/radiation effects; Tumor Cells, Cultured; Cxcl12; glioblastoma; mesenchymal activation; radioresistance; subventricular zone  
  Abstract 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.  
  Address Laboratory of Developmental Neurobiology, GIGA-Neurosciences Research Center, University of Liege, Liege, Belgium (N.G., A.L., J.N., M.D., E.W., B.R.); Department of Neurosurgery, CHU and University of Liege, Liege, Belgium (A.L., D.M.); Department of Radiotherapy and Oncology, CHU and University of Liege, Liege, Belgium (F.L., P.M.); Laboratory of Tumor and Development Biology, GIGA-Cancer Research Center, University of Liege, Liege, Belgium (F.L.); Cyclotron Research Centre, University of Liege, Liege, Belgium (F.L.); Human Genetics, CHU and University of Liege, Liege, Belgium (N.G., J.K., V.B.); Department of Neurosurgery, Brain Center Rudolf Magnus Institute of Neurosciences and the T&P Bohnenn Laboratory for Neuro-Oncology University Medical Center, Utrecht, The Netherlands (N.G., J.K., S.B., P.R.); GIGA-Viral Vector Plateform, University of Liege, Liege, Belgium (E.D.V.); Department of Neurology, CHU and University of Liege, Liege, Belgium (P.M., B.R.)  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1522-8517 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27370398 Approved no  
  Call Number ref @ user @ Serial 96647  
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