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Versican isoform V1 regulates proliferation and migration in high-grade gliomas

  • Laboratory Investigation
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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.

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Acknowledgments

We thank Birgit Jachnik and Ina Weig-Meckl for excellent technical assistance.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Wilhelm Sander-NeuroOncology Unit and Department of Neurology, University Hospital, Franz Josef Strauß-Allee 11, 93053, Regensburg, Germany

    Julia Onken, Sylvia Moeckel, Petra Leukel, Verena Leidgens, Fusun Baumann, Ulrich Bogdahn, Arabel Vollmann-Zwerenz & Peter Hau

  2. Department of Neurosurgery, Charité University Medicine Berlin, Hindenburgdamm 30, 12203, Berlin, Germany

    Julia Onken

  3. Department of Neurology, Royal Brisbane and Women’s Hospital, Herston, QLD, 4029, Australia

    Fusun Baumann

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  1. Julia Onken
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Correspondence to Peter Hau.

Additional information

Arabel Vollmann-Zwerenz and Peter Hau have contributed equally to this work.

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Supplementary Fig. 1

A specific siRNA against V3 was constructed that yielded a significant effect in regulating V3 as compared to untreated, scrambled siRNA and lipofectamine controls (a). No off-target effects of siRNA V3 on V1 or V3 mRNA were observed (b). *p < 0.05

Supplementary Fig. 2

Results of siV1 were verified in HTZ-349, A172, and U87MG cell lines for proliferation and migration. Proliferation is decreased notably (a) with a predominant effect in HTZ-349, whereas scratch (b) and Boyden chamber assays (c) yielded similar effects in all three cell lines. Of note, U87 is V2-negative, excluding an effect of V2

Supplementary Fig. 3

Results of siV1 were verified in HTZ-349, A172, and U87MG cell lines for proliferation and migration. Proliferation is decreased notably (a) with a predominant effect in HTZ-349, whereas scratch (b) and Boyden chamber assays (c) yielded similar effects in all three cell lines. Of note, U87 is V2-negative, excluding an effect of V2

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Onken, J., Moeckel, S., Leukel, P. et al. Versican isoform V1 regulates proliferation and migration in high-grade gliomas. J Neurooncol 120, 73–83 (2014). https://doi.org/10.1007/s11060-014-1545-8

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