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

  • Lab. investigation - human/animal tissue
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Abstract

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.

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Acknowledgments

This research was supported by NIH grants #NS-36674-08, NS-3080011 and CA10373602 to R.H.M. F98 and U87 cells were provided by Dr. Steven M. Greenberg (Roswell Park Cancer Institute). We would like to thank Anita Zaremba for technical assistance with slice culture preparation.

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Authors and Affiliations

  1. Department of Neurology, University Hospital of Cleveland, Hanna House 5, 11100 Euclid Avenue, Cleveland, OH, 44106, USA

    Stephen M. Selkirk

  2. Department of Neurosurgery, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14216, USA

    Jay Morrow, Tara A. Barone & Robert J. Plunkett

  3. Department of Neurosurgery, University Hospital of Cleveland, 11100 Euclid Avenue, Cleveland, OH, 44106, USA

    Alan Hoffer

  4. Department of Neuroscience, Case Western School of Medicine, Cleveland, OH, USA

    Jeffrey Lock, Anne DeChant, Saisho Mangla & Robert H. Miller

  5. Departments of Neurosurgery, State University of New York at Buffalo, 100 High Street, E-2, Buffalo, NY, 14203, USA

    Robert J. Plunkett

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  1. Stephen M. Selkirk
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Correspondence to Stephen M. Selkirk.

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Selkirk, S.M., Morrow, J., Barone, T.A. et al. Elevation of osteopontin levels in brain tumor cells reduces burden and promotes survival through the inhibition of cell dispersal. J Neurooncol 86, 285–296 (2008). https://doi.org/10.1007/s11060-007-9477-1

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  • DOI: https://doi.org/10.1007/s11060-007-9477-1

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