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Selective osteopontin knockdown exerts anti‐tumoral activity in a human glioblastoma model
Author(s) -
Lamour Virginie,
Le Mercier Marie,
Lefranc Florence,
Hagedorn Martin,
Javerzat Sophie,
Bikfalvi Andreas,
Kiss Robert,
Castronovo Vincent,
Bellahcène Akeila
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24751
Subject(s) - osteopontin , glioma , u87 , cancer research , gene knockdown , small interfering rna , angiogenesis , transfection , biology , in vivo , cell culture , in vitro , integrin , chemistry , cell , immunology , biochemistry , genetics , microbiology and biotechnology
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.