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The biological role and regulation of versican levels in cancer

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Abstract

Increased expression of the proteoglycan, versican is strongly associated with poor outcome for many different cancers. Depending on the cancer type, versican is expressed by either the cancer cells themselves or by stromal cells surrounding the tumor. Versican plays diverse roles in cell adhesion, proliferation, migration and angiogenesis, all features of invasion and metastasis. These wide ranging functions have been attributed to the central glycosaminoglycan-binding region of versican, and to the N-(G1) and C-(G3) terminal globular domains which collectively interact with a large number of extracellular matrix and cell surface structural components. Here we review the recently identified mechanisms responsible for the regulation of versican expression and the biological roles that versican plays in cancer invasion and metastasis. The regulation of versican expression may represent one mechanism whereby cancer cells alter their surrounding microenvironment to facilitate the malignant growth and invasion of several tumor types. A greater understanding of the regulation of versican expression may contribute to the development of therapeutic methods to inhibit versican function and tumor invasion.

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Acknowledgements

This work was supported by the National Health Medical Research Council Grants #519228 and #349457, University of Adelaide Faculty of Health Sciences (Hilda Farmer Research Fellowship to CR) and the Cancer Council South Australia grants and fellowships (W Bruce Hall Cancer Research Fellowship to AJS and Senior Research Fellowship to CR).

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  1. Andrew J. Sakko

    Present address: Novozymes Biopharma AU Limited, 28 Dalgleish Street, Thebarton, SA, 5031, Australia

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  1. Research Centre for Reproductive Health, Discipline of Obstetrics and Gynaecology, University of Adelaide, Adelaide, SA, 5005, Australia

    Carmela Ricciardelli, Andrew J. Sakko, Miranda P. Ween & Darryl L. Russell

  2. Dame Roma Mitchell Cancer Research Laboratories, University of Adelaide, Hanson Institute, Adelaide, SA, 5000, Australia

    Carmela Ricciardelli, Andrew J. Sakko & David J. Horsfall

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Ricciardelli, C., Sakko, A.J., Ween, M.P. et al. The biological role and regulation of versican levels in cancer. Cancer Metastasis Rev 28, 233–245 (2009). https://doi.org/10.1007/s10555-009-9182-y

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