Elevation of osteopontin levels in brain tumor cells reduces burden and promotes survival through the inhibition of cell dispersal

Osteopontin (OPN) is a pleotrophic molecule that has been associated with multiple disorders of the central nervous system (CNS). Its roles in CNS malignancy are unclear but suggest that higher levels of OPN expression correlate with increased tumor grade and increased migratory capacity of tumor ce...

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Bibliographic Details
Published in:Journal of neuro-oncology 2008-02, Vol.86 (3), p.285-296
Main Authors: Selkirk, Stephen M., Morrow, Jay, Barone, Tara A., Hoffer, Alan, Lock, Jeffrey, DeChant, Anne, Mangla, Saisho, Plunkett, Robert J., Miller, Robert H.
Format: Article
Language:English
Subjects:
Animals
Apoptosis - physiology
Brain Neoplasms - metabolism
Brain Neoplasms - mortality
Brain Neoplasms - physiopathology
Bromodeoxyuridine - metabolism
Cell Line, Tumor
Cell Movement - physiology
Cell Proliferation
Gene Expression Regulation, Neoplastic - genetics
Gene Expression Regulation, Neoplastic - physiology
Glioblastoma - metabolism
Glioblastoma - mortality
Glioblastoma - physiopathology
Glioma - metabolism
Glioma - mortality
Glioma - physiopathology
Green Fluorescent Proteins - metabolism
Humans
In Situ Nick-End Labeling
Lab. Investigation - Human/Animal Tissue
Medicine
Medicine & Public Health
Neurology
Oncology
Osteopontin - genetics
Osteopontin - metabolism
Platelet Endothelial Cell Adhesion Molecule-1 - metabolism
Rats
Survival Analysis
Time Factors
Transfection
Transplants
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Summary:Osteopontin (OPN) is a pleotrophic molecule that has been associated with multiple disorders of the central nervous system (CNS). Its roles in CNS malignancy are unclear but suggest that higher levels of OPN expression correlate with increased tumor grade and increased migratory capacity of tumor cells. In this study OPN cDNA was cloned into a retroviral vector and used to infect F98 Fischer rat-derived glioma cells and U87 human-derived glioblastoma multiforme (GBM) cells in vitro. Cells expressing high levels of OPN migrated less distance than control cells in vitro. This effect was not RGD mediated, but was reversed in the presence of c-Jun N-terminal kinase (JNK) inhibitor suggesting that JNK1 is an essential component of a negative feedback loop affecting OPN activated signaling cascades. Implantation of tumor cells expressing high levels of OPN into adult Fischer rats and nude rats resulted in morphologically distinct tumors and prolonged host survival relative to controls. We propose that local produced, high level OPN expression limits the malignant character of glioma cells and that the downstream mechanisms involved represent pathways that may have therapeutic value in the treatment of human CNS malignancy.
ISSN:0167-594X
1573-7373
DOI:10.1007/s11060-007-9477-1