Abstract
Glioblastomas (GBM) are the most frequent and malignant human brain tumor type. Typically striking in adulthood, tumor progression is rapid, relentless, and ultimately leads to the patient's death within a year of diagnosis. The identification of transcriptionally regulated genes can lead to the discovery of targets for antibody or small-molecule-mediated therapy, as well as diagnostic markers. We prepared cDNA arrays that are specifically enriched for genes expressed in human brain tumors and profiled gene expression patterns in 14 individual tumor samples. Out of 25 000 clones arrayed, greater than 200 genes were found transcriptionally induced in glioblastomas compared to normal human brain tissue including the receptor tyrosine phosphataseζ (RPTPζ) and one of its ligands, pleiotrophin (Ptn). We confirmed by Northern blot analysis and immunohistochemistry that RPTPζ is enriched in tumor samples. Knockdown of RPTPζ by RNA interference studies established a functional role of RPTPζ in cell migration. Our results suggest a novel function for RPTPζ in regulating glioblastoma cell motility and point to the therapeutic utility of RPTPζ as a target for antibody-mediated therapy of brain tumors.
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Abbreviations
- GBM:
-
glioblastoma
- Ptn:
-
pleiotrophin
- RPTPζ:
-
receptor protein tyrosine phosphatase zeta
- siRNA:
-
short interfering RNA
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Acknowledgements
We thank Karoly Nikolich for his continued enthusiastic support and guidance, and helpful comments on the manuscript. We thank all our colleagues at AGY Therapeutics for their critical contributions. We also like to thank Darell Bigner for fruitful discussions, experimental advice and the kind gift of the D566 Glioblastoma cell line. This study was supported by DFG We 928/4-1 to MW.
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Müller, S., Kunkel, P., Lamszus, K. et al. A role for receptor tyrosine phosphataseζ in glioma cell migration. Oncogene 22, 6661–6668 (2003). https://doi.org/10.1038/sj.onc.1206763
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DOI: https://doi.org/10.1038/sj.onc.1206763
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