title: MTSS1 is epigenetically regulated in glioma cells and inhibits glioma cell motility.
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.
authors.affiliation: Department of Neuropathology, University of Bonn, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Luxen
authors.affiliation: Department of Neuropathology, University of Bonn, Germany.
authors.forename: Gerrit H
authors.initials: GH
authors.lastname: Gielen
authors.affiliation: Department of Neuropathology, University of Bonn, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Waha
authors.affiliation: Department of Neuropathology, University of Bonn, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Isselstein
authors.affiliation: Department of Neuropathology, University of Bonn, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Müller
authors.affiliation: Institute of Reconstructive Neurobiology, LIFE & BRAIN, University of Bonn, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Koch
authors.affiliation: Department of Neuropathology, University of Bonn, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hammes
authors.affiliation: Department of Neuropathology, University of Bonn, Germany.
authors.forename: Albert
authors.initials: A
authors.lastname: Becker
authors.affiliation: Institute of Neurosurgery, University of Bonn, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Simon
authors.affiliation: Department of Molecular Medicine and Experimental Immunology, (Core Facility Flow Cytometry) University of Bonn, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Wurst
authors.affiliation: Department of Molecular Medicine and Experimental Immunology, (Core Facility Flow Cytometry) University of Bonn, Germany.
authors.forename: Elmar
authors.initials: E
authors.lastname: Endl
authors.affiliation: Department of Neuropathology, University of Bonn, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Pietsch
authors.affiliation: Department of Neuropathology, University of Bonn, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Gessi
authors.affiliation: Department of Neuropathology, University of Bonn, Germany. Electronic address: awaha@uni-bonn.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Waha