MTSS1 is epigenetically regulated in glioma cells and inhibits glioma cell motility |
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Authors: | Daniel Luxen Gerrit H Gielen Anke Waha Lukas Isselstein Tim Müller Philipp Koch Jennifer Hammes Albert Becker Matthias Simon Peter Wurst Elmar Endl Torsten Pietsch Marco Gessi Andreas Waha |
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Institution: | 2. Institute of Neurosurgery, University of Bonn, Germany;4. Department of Molecular Medicine and Experimental Immunology, (Core Facility Flow Cytometry) University of Bonn, Germany |
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Abstract: | Epigenetic silencing by DNA methylation in brain tumors has been reported for many genes, however, their function on pathogenesis needs to be evaluated. We investigated the MTSS1 gene, identified as hypermethylated by differential methylation hybridization (DMH). Fifty-nine glioma tissue samples and seven glioma cell lines were examined for hypermethylation of the MTSS1 promotor, MTSS1 expression levels and gene dosage. GBM cell lines were treated with demethylating agents and interrogated for functional consequences of MTSS1 expression after transient transfection. Hypermethylation was significantly associated with IDH1/2 mutation. Comparative SNP analysis indicates higher incidence of loss of heterozygosity of MTSS1 in anaplastic astrocytomas and secondary glioblastomas as well as hypermethylation of the remaining allele. Reversal of promoter hypermethylation results in an increased MTSS1 expression. Cell motility was significantly inhibited by MTSS1 overexpression without influencing cell growth or apoptosis. Immunofluorescence analysis of MTSS1 in human astrocytes indicates co-localization with actin filaments. MTSS1 is down-regulated by DNA methylation in glioblastoma cell lines and is part of the G-CIMP phenotype in primary glioma tissues. Our data on normal astrocytes suggest a function of MTSS1 at focal contact structures with an impact on migratory capacity but no influence on apoptosis or cellular proliferation. |
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Keywords: | Address all correspondence to Andreas Waha PhD Department of Neuropathology University of Bonn Medical Center Sigmund-Freud-Str 25 D-53105 Bonn Germany |
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