Selective osteopontin knockdown exerts anti-tumoral activity in a human glioblastoma model.
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.
Lamour
Virginie
V
Metastasis Research Laboratory, GIGA-Cancer, University of Liège, Liège, Belgium.
Le Mercier
Marie
M
Laboratory of Toxicology, Institute of Pharmacy, Free University of Brussels, Brussels, Belgium.
Lefranc
Florence
F
Laboratory of Toxicology, Institute of Pharmacy, Free University of Brussels, Brussels, Belgium.
Hagedorn
Martin
M
INSERM U920.|University of Bordeaux, Talence, F-33405, France.
Javerzat
Sophie
S
INSERM U920.|University of Bordeaux, Talence, F-33405, France.
Bikfalvi
Andreas
A
INSERM U920.|University of Bordeaux, Talence, F-33405, France.
Kiss
Robert
R
Laboratory of Toxicology, Institute of Pharmacy, Free University of Brussels, Brussels, Belgium.
Castronovo
Vincent
V
Metastasis Research Laboratory, GIGA-Cancer, University of Liège, Liège, Belgium.
Bellahcène
Akeila
A
Metastasis Research Laboratory, GIGA-Cancer, University of Liège, Liège, Belgium.
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002642:Chick Embryo; D004797:Enzyme-Linked Immunosorbent Assay; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D009389:Neovascularization, Pathologic / Q000235:genetics; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D034741:RNA, Small Interfering; D053495:Osteopontin