Brain 2014.pdfVIP

BRAIN A JOURNAL OF NEUROLOGY Thymosin beta 4 gene silencing decreases stemness and invasiveness in glioblastoma Hans-Georg Wirsching,1,2 Shanmugarajan Krishnan,1,2 Ana-Maria Florea,3 Karl Frei,2,4 Niklaus Krayenbu?hl,4 Kathy Hasenbach,1 Guido Reifenberger,3 Michael Weller1,2 and Ghazaleh Tabatabai1,2 1 Department of Neurology, Laboratory of Molecular Neuro-Oncology, University Hospital Zurich, Zurich, Switzerland 2 Neuroscience Centre Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland 3 Department of Neuropathology, Heinrich Heine University Du?sseldorf and German Cancer Consortium (DKTK), Du?sseldorf, Germany 4 Department of Neurosurgery, University Hospital Zurich, Zurich, Switzerland Correspondence to: Ghazaleh Tabatabai, MD PhD, Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, 8091 Zurich, Switzerland E-mail: ghazaleh.tabatabai@usz.ch Thymosin beta 4 is a pleiotropic actin-sequestering polypeptide that is involved in wound healing and developmental processes. Thymosin beta 4 gene silencing promotes differentiation of neural stem cells whereas thymosin beta 4 overexpression initiates cortical folding of developing brain hemispheres. A role of thymosin beta 4 in malignant gliomas has not yet been investigated. We analysed thymosin beta 4 staining on tissue microarrays and performed interrogations of the REMBRANDT and the Cancer Genome Atlas databases. We investigated thymosin beta 4 expression in seven established glioma cell lines and seven glioma- initiating cell lines and induced or silenced thymosin beta 4 expression by lentiviral transduction in LNT-229, U87MG and GS-2 cells to study the effects of altered thymosin beta 4 expression on gene expression, growth, clonogenicity, migration, invasion, self-renewal and differentiation capacity in vitro, and tumorigenicity in vivo. Thymosin beta 4 expression increased with grade of malignancy in gliomas. Thymosin beta 4 gene silencing in LNT-229 and U87MG glioma cells inhibit