CXCL12; cancer stem cells; invasion; stem cell microenvironment
Abstract :
[en] BACKGROUND: Patients with glioblastoma multiforme (GBM) have an overall median survival of 15 months. This catastrophic survival rate is the consequence of systematic relapses that could arise from remaining glioblastoma stem cells (GSCs) left behind after surgery. We previously demonstrated that GSCs are able to escape the tumor mass and specifically colonize the adult subventricular zones (SVZs) after transplantation. This specific localization, away from the initial injection site, therefore represents a high-quality model of a clinical obstacle to therapy and relapses because GSCs notably retain the ability to form secondary tumors. METHOD: In this work, we questioned the role of the CXCL12/CXCR4 signaling in the GSC-specific invasion of the SVZs. RESULTS: We demonstrated that both receptor and ligand are respectively expressed by different GBM cell populations and by the SVZ itself. In vitro migration bio-assays highlighted that human U87MG GSCs isolated from the SVZs (U87MG-SVZ) display stronger migratory abilities in response to recombinant CXCL12 and/or SVZ-conditioned medium (SVZ-CM) compared with cancer cells isolated from the tumor mass (U87MG-TM). Moreover, in vitro inhibition of the CXCR4 signaling significantly decreased the U87MG-SVZ cell migration in response to the SVZ-CM. Very interestingly, treating U87MG-xenografted mice with daily doses of AMD3100, a specific CXCR4 antagonist, prevented the specific invasion of the SVZ. Another in vivo experiment, using CXCR4-invalidated GBM cells, displayed similar results. CONCLUSION: Taken together, these data demonstrate the significant role of the CXCL12/CXCR4 signaling in this original model of brain cancer invasion.
Disciplines :
Neurology 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
KROONEN, Jérôme ; Centre Hospitalier Universitaire de Liège - CHU > Centre d'oncologie
Di Valentin, Emmanuel ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Virologie et immunologie
Denne, Alexandre ; Université de Liège - ULiège > Master méd. (ex 4e master en 4 ans)
Martinive, Philippe ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Rogister, Bernard ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, et biochimie humaine
Language :
English
Title :
Adult mouse subventricular zones stimulate glioblastoma stem cells specific invasion through CXCL12/CXCR4 signaling.
Publication date :
2015
Journal title :
Neuro-Oncology
ISSN :
1522-8517
eISSN :
1523-5866
Publisher :
Oxford University Press
Volume :
17
Issue :
1
Pages :
81-94
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
(c) The Author(s) 2014. 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.
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