1. ¹Department of Neurology, University of Regensburg, Universitaetsstrasse 84, Regensburg 93053, Germany
2. ²Institute of Basic Medical Sciences, University of Oslo, Sognsvannsveien 9, Oslo 0317, Norway
3. ³Institute of Pathology, University of Regensburg, Franz-Josef-Strau-Allee 11, Regensburg 93053, Germany
4. ⁴Department of Psychiatry and Psychotherapy, RWTH Aachen University, Pauwelsstrasse 30, Aachen 52074, Germany

Correspondence: Dr P Hau, E-mail: peter.hau@medbo.de

Received 13 November 2006; Revised 20 February 2007; Accepted 2 April 2007; Published online 24 April 2007.

Abstract

Versican is a large chondroitin sulphate proteoglycan produced by several tumour cell types, including high-grade glioma. The increased expression of certain versican isoforms in the extracellular matrix (ECM) plays a role in tumour cell growth, adhesion and migration. Transforming growth factor-2 (TGF-2) is an important modulator of glioma invasion, partially by remodeling the ECM. However, it is unknown whether it interacts with versican during malignant progression of glioma cells. Here, we analysed the effect of TGF-2 on the expression of versican isoforms. The expression of versican V0/V1 was upregulated by TGF-2 detected by quantitative polymerase chain reaction and immunoprecipitation, whereas V2 was not induced. Using time-lapse scratch and spheroid migration assays, we observed that the glioma migration rate is significantly increased by exogenous TGF-2 and inhibited by TGF-2-specific antisense oligonucleotides. Interestingly, an antibody specific for the DPEAAE region of glycosaminoglycan- domain of versican was able to reverse the effect of TGF-2 on glioma migration in a dose-dependent manner. Taken together, we report here that TGF-2 triggers the malignant phenotype of high-grade gliomas by induction of migration, and that this effect is, at least in part, mediated by versican V0/V1.