title: Selective osteopontin knockdown exerts anti-tumoral activity in a human glioblastoma model.
abstract: 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.
authors.affiliation: Metastasis Research Laboratory, GIGA-Cancer, University of Liège, Liège, Belgium.
authors.forename: Virginie
authors.initials: V
authors.lastname: Lamour
authors.affiliation: Laboratory of Toxicology, Institute of Pharmacy, Free University of Brussels, Brussels, Belgium.
authors.forename: Marie
authors.initials: M
authors.lastname: Le Mercier
authors.affiliation: Laboratory of Toxicology, Institute of Pharmacy, Free University of Brussels, Brussels, Belgium.
authors.forename: Florence
authors.initials: F
authors.lastname: Lefranc
authors.affiliation: INSERM U920.|University of Bordeaux, Talence, F-33405, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Hagedorn
authors.affiliation: INSERM U920.|University of Bordeaux, Talence, F-33405, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Javerzat
authors.affiliation: INSERM U920.|University of Bordeaux, Talence, F-33405, France.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bikfalvi
authors.affiliation: Laboratory of Toxicology, Institute of Pharmacy, Free University of Brussels, Brussels, Belgium.
authors.forename: Robert
authors.initials: R
authors.lastname: Kiss
authors.affiliation: Metastasis Research Laboratory, GIGA-Cancer, University of Liège, Liège, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Castronovo
authors.affiliation: Metastasis Research Laboratory, GIGA-Cancer, University of Liège, Liège, Belgium.
authors.forename: Akeila
authors.initials: A
authors.lastname: Bellahcène
mesh_terms: 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
chemical_list: D034741:RNA, Small Interfering; D053495:Osteopontin