Article (Scientific journals)
Targeting osteopontin suppresses glioblastoma stem-like cell character and tumorigenicity in vivo
Lamour, Virginie; Henry, Aurélie; Kroonen, Jerome et al.
2015In International Journal of Cancer
Peer Reviewed verified by ORBi
 

Files


Full Text
ijc29454.pdf
Author preprint (1.81 MB)
Request a copy

All documents in ORBi are protected by a user license.

Send to



Details



Keywords :
EGFR; Osteopontin; Sox2; Glioblastoma; Tumor initiating cells
Abstract :
[en] Osteopontin (OPN) is a secreted protein involved in most aspects of tumor progression and metastasis development. Elevated OPN expression has been reported in multiple types of cancer including glioblastoma (GBM), the highest grade and most aggressive brain tumor. GBMs contain a subpopulation of glioma-initiating cells (GICs) implicated in progression, therapeutic resistance and recurrence. We have previously demonstrated that OPN silencing inhibited GBM cell growth in vitro and in vivo. Moreover, activation of CD44 signaling upon OPN ligation has been recently implicated in the acquisition of a stem cell phenotype by GBM cells. The present study is aimed to explore OPN autocrine function using shRNA silencing strategy in GICs enriched from GBM cell lines and a human primary GBM grown in EGF and bFGF defined medium. The removal of these growth factors and addition of serum induced a significant loss of OPN expression in GICs. We showed that OPN-silenced GICs were unable to grow as spheres and this capacity was restored by exogenous OPN. Importantly, the expression of Sox2, Oct3/4 and Nanog, key stemness transcription factors, was significantly decreased in GICs upon OPN targeting. We identified Akt/mTOR/p70S6K as the main signaling pathway triggered following OPN-mediated EGFR activation in GICs. Finally, in an orthotopic xenograft mouse model, the tumorigenic potential of U87-MG sphere cells was completely abrogated upon OPN silencing. Our demonstration of endogenous OPN major regulatory effects on GICs stemness phenotype and tumorigenicity implies a greater role than anticipated for OPN in GBM pathogenesis from initiation and progression to probable recurrence.
Disciplines :
Neurology
Oncology
Author, co-author :
Lamour, Virginie
Henry, Aurélie ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Kroonen, Jerome
Nokin, Marie-Julie  ;  Université de Liège - ULiège > Form. doc. sc. bioméd. & pharma.
von Marschall, Zofia
Fisher, Larry
Chau, Tieu-Lan ;  Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Chariot, Alain ;  Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Sanson, Marc
Delattre, Jean-Yves
Turtoi, Andrei ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Peulen, Olivier  ;  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
Castronovo, Vincenzo ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire
Bellahcene, Akeila ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
More authors (5 more) Less
Language :
English
Title :
Targeting osteopontin suppresses glioblastoma stem-like cell character and tumorigenicity in vivo
Publication date :
24 January 2015
Journal title :
International Journal of Cancer
ISSN :
0020-7136
eISSN :
1097-0215
Publisher :
Wiley Liss, Inc., New York, United States - New York
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 04 March 2015

Statistics


Number of views
115 (40 by ULiège)
Number of downloads
10 (10 by ULiège)

Scopus citations®
 
42
Scopus citations®
without self-citations
41
OpenCitations
 
42

Bibliography


Similar publications



Contact ORBi