[en] Osteopontin (OPN), a member of the SIBLING (Small Integrin-Binding LIgand N-linked Glycoprotein) family, is overexpressed in human glioblastoma. Higher levels of OPN expression correlate with increased tumor grade and enhanced migratory capacity of tumor cells. Based on these observations, we explored the possibility that knocking down OPN expression in glioblastoma cells could exert an anti-tumoral activity using an avian in vivo glioblastoma model that mimics closely human gliobastoma. Human U87-MG glioma cells transfected with specific anti-OPN small interfering RNAs (siRNAs) were grafted onto the chicken chorio-allantoic membrane (CAM). OPN-deficient U87-MG cells gave rise to tumors that were significantly smaller than tumors formed from untransfected cells (paired t-test, p<0.05). Accordingly, the amount of proliferating cells in OPN-deficient tumors showed a six-fold reduction when compared to control tumors. However, OPN inhibition did not affect significantly tumor-associated angiogenesis. In vitro, OPN-silenced U87-MG and U373-MG cells showed decreased motility and migration. This is the first demonstration that OPN inhibition blocks glioma tumor growth, making this invasion-related protein an attractive target for glioma therapy. (c) 2009 UICC.
Lamour, Virginie ; Université de Liège - ULiège > Centre facultaire de rech. en cancérologie expérimentale
Le Mercier, M.
Lefranc, F.
Hagedorn, M.
Javerzat, S.
Bikfalvi, A.
Kiss, R.
Castronovo, Vincenzo ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire - GIGA-R : Labo de recherche sur les métastases
Bellahcene, Akeila ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Language :
English
Title :
Selective osteopontin knockdown exerts anti-tumoral activity in a human glioblastoma model.
Publication date :
2010
Journal title :
International Journal of Cancer
ISSN :
0020-7136
eISSN :
1097-0215
Publisher :
Wiley Liss, Inc., New York, United States - New York
Volume :
126
Pages :
1797-1805
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
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