The role of versican isoforms V0/V1 in glioma migration mediated by transforming growth factor-beta2.
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-beta2 (TGF-beta2) 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-beta2 on the expression of versican isoforms. The expression of versican V0/V1 was upregulated by TGF-beta2 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-beta2 and inhibited by TGF-beta2-specific antisense oligonucleotides. Interestingly, an antibody specific for the DPEAAE region of glycosaminoglycan-beta domain of versican was able to reverse the effect of TGF-beta2 on glioma migration in a dose-dependent manner. Taken together, we report here that TGF-beta2 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.
Arslan
F
F
Department of Neurology, University of Regensburg, Universitaetsstrasse 84, Regensburg 93053, Germany.
Bosserhoff
A-K
AK
Nickl-Jockschat
T
T
Doerfelt
A
A
Bogdahn
U
U
Hau
P
P
D002465:Cell Movement / Q000187:drug effects*; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000473:pathology*; D006801:Humans; D009361:Neoplasm Invasiveness; D020033:Protein Isoforms / Q000502:physiology; D053781:Transforming Growth Factor beta2 / Q000235:genetics / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D053675:Versicans / Q000235:genetics / Q000502:physiology*
D020033:Protein Isoforms; D053781:Transforming Growth Factor beta2; C508322:VCAN protein, human; D053675:Versicans