title: Versican isoform V1 regulates proliferation and migration in high-grade gliomas.
abstract: Versican is a large chondroitin sulphate proteoglycan produced by several tumor cell types, including high-grade gliomas. Increased expression of distinct versican isoforms in the extracellular matrix plays a role in tumor cell growth, adhesion and migration. We have recently shown that transforming growth factor (TGF-beta)2, an important modulator of glioma invasion, interacts with versican isoforms V0/V1 during malignant progression of glioma in vitro. However, the distinct subtype of versican that modulates these effects could not be specified. Here, we show that transient down-regulation of V1 by siRNA leads to a significant reduction of proliferation and migration in glioblastoma cell lines and glioblastoma progenitor cells, whereas tumor cell attachment stays unaffected. We conclude that V1 plays a predominant role in modulating central pathophysiological mechanisms as proliferation and migration in glioblastoma. Considering that TGF-beta is a master regulator of glioma pathophysiology, and that V0/1 is induced by TGF-beta2, therapeutic regulation of V1 may induce meaningful effects on glioma cell migration not only in vitro, but also in vivo.
authors: Wilhelm Sander-NeuroOncology Unit and Department of Neurology, University Hospital, Franz Josef Strauß-Allee 11, 93053, Regensburg, Germany.
authors: Julia
authors: J
authors: Onken
authors: Sylvia
authors: S
authors: Moeckel
authors: Petra
authors: P
authors: Leukel
authors: Verena
authors: V
authors: Leidgens
authors: Fusun
authors: F
authors: Baumann
authors: Ulrich
authors: U
authors: Bogdahn
authors: Arabel
authors: A
authors: Vollmann-Zwerenz
authors: Peter
authors: P
authors: Hau
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D005109:Extracellular Matrix; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D060787:Neoplasm Grading; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059008:Time-Lapse Imaging; D053781:Transforming Growth Factor beta2 / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D053675:Versicans / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D053781:Transforming Growth Factor beta2; D053675:Versicans