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Deficiency of the protein-tyrosine phosphatase DEP-1/PTPRJ promotes matrix metalloproteinase-9 expression in meningioma cells

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Abstract

Brain-invasive growth of a subset of meningiomas is associated with less favorable prognosis. The molecular mechanisms causing invasiveness are only partially understood, however, the expression of matrix metalloproteinases (MMPs) has been identified as a contributing factor. We have previously found that loss of density enhanced phosphatase-1 (DEP-1, also designated PTPRJ), a transmembrane protein-tyrosine phosphatase, promotes meningioma cell motility and invasive growth in an orthotopic xenotransplantation model. We have now analyzed potential alterations of the expression of genes involved in motility control, caused by DEP-1 loss in meningioma cell lines. DEP-1 depleted cells exhibited increased expression of mRNA encoding MMP-9, and the growth factors EGF and FGF-2. The increase of MMP-9 expression in DEP-1 depleted cells was also readily detectable at the protein level by zymography. MMP-9 upregulation was sensitive to chemical inhibitors of growth factor signal transduction. Conversely, MMP-9 mRNA levels could be stimulated with growth factors (e.g. EGF) and inflammatory cytokines (e.g. TNFα). Increase of MMP-9 expression by DEP-1 depletion, or growth factor/cytokine stimulation qualitatively correlated with increased invasiveness in vitro scored as transmigration through matrigel-coated membranes. The studies suggest induction of MMP-9 expression promoted by DEP-1 deficiency, or potentially by growth factors and inflammatory cytokines, as a mechanism contributing to meningioma brain invasiveness.

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Acknowledgments

We are grateful to Anita Lal for kind provision of meningioma cell lines. This work was supported by funding of the Deutsche Forschungsgemeinschaft (SFB604 A1 to F.D.B and C.M., BO 1043/9-1, and MA2530/6-1) and the Wilhelm Sander Stiftung (to C.M. 2014.092.1.).

Conflict of interest

The authors declare that there is no conflict of interest.

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Authors and Affiliations

  1. Institute of Molecular Cell Biology, CMB, Jena University Hospital, Hans-Knöll-Strasse 2, 07745, Jena, Germany

    Astrid Petermann, Yvonn Stampnik & Frank-D. Böhmer

  2. Leibnitz Institute for Age Research, Fritz Lipmann Institute, Jena, Germany

    Yan Cui & Helen Morrison

  3. Institute of Neuropathology, University Hospital Magdeburg, Otto-von-Guericke-University Magdeburg, Leipziger Strasse 44, 39120, Magdeburg, Germany

    Doreen Pachow, Nadine Kliese & Christian Mawrin

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  1. Astrid Petermann
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Correspondence to Christian Mawrin or Frank-D. Böhmer.

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Petermann, A., Stampnik, Y., Cui, Y. et al. Deficiency of the protein-tyrosine phosphatase DEP-1/PTPRJ promotes matrix metalloproteinase-9 expression in meningioma cells. J Neurooncol 122, 451–459 (2015). https://doi.org/10.1007/s11060-015-1740-2

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  • DOI: https://doi.org/10.1007/s11060-015-1740-2

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