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Soluble cadherins as cancer biomarkers

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Abstract

Molecular activities, regulating a balanced tissue organisation, are frequently disturbed during cancer progression. These include protein ectodomain shedding, a post-translational process that substantially changes the functional properties of the substrate protein. In comparison with normal epithelia, cancer cells almost invariably show diminished cadherin-mediated intercellular adhesion. This review will address cadherin ectodomain shedding and its functional consequence in normal physiology and in the tumor environment. Soluble cadherin fragments may retain specific biological activities during cancer cell invasion, angiogenesis and perineural invasion. When diffusion barriers disappear, soluble cadherins are detected in sera from cancer patients. Soluble N-(neural) cadherin may represent a novel diagnosis/prognostic biomarker showing a correlation with PSA in sera of prostate cancer patients. Furthermore, therapeutic monitoring in pancreas adenomacarcinoma revealed a correlation between circulating soluble N-cadherin and CA 19-9. A better understanding of cadherin regulation in cancer progression will likely increase our awareness of the importance of the combinatorial signals that regulate tissue integrity and eventually result in the identification of new therapeutics targeting cadherins.

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Acknowledgements

G. De Bruyne and J. Roels are gratefully acknowledged for preparation of the illustrations. This work was funded by Fonds Wetenschappelijk Onderzoek (FWO)-Vlaanderen (Brussels, Belgium), Geconcerteerde Onderzoek Aangelegenheden (GOA, University Ghent, Belgium) and by the Sixth Framework program of the European Community (METABRE, LSHC-CT-2004-503049). O. De Wever was supported by METABRE and Bijzonder Onderzoeks Fonds (BOF, University Ghent, Belgium). L. Derycke was supported by FYTOES (Federale Overheidsdienst Volksgezondheid, Veiligheid voor de Voedselketen en Leefmilieu, Brussels, Belgium). A. Hendrix was supported by a fellowship from the ‘Stichting Emmanuel van der Schueren’.

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Authors and Affiliations

  1. Laboratory of Experimental Cancer Research, University Hospital Ghent, De Pintelaan 185, 9000, Gent, Belgium

    Olivier De Wever, Lara Derycke & Marc Bracke

  2. Department of Medical Oncology, University Hospital Ghent, De Pintelaan 185, 9000, Gent, Belgium

    An Hendrix

  3. Department of Radiotherapy and Nuclear Medicine, University Hospital Ghent, De Pintelaan 185, 9000, Gent, Belgium

    Gert De Meerleer

  4. INSERM U515, Hôpital Saint-Antoine, Rue du Faubourg 184, 75571, Paris, France

    François Godeau

  5. Department of Gynaecology, University Hospital Ghent, De Pintelaan 185, 9000, Gent, Belgium

    Herman Depypere

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  1. Olivier De Wever
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  2. Lara Derycke
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  3. An Hendrix
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  4. Gert De Meerleer
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  5. François Godeau
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  6. Herman Depypere
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  7. Marc Bracke
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Corresponding author

Correspondence to Marc Bracke.

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Olivier De Wever and Lara Derycke have contributed equally.

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De Wever, O., Derycke, L., Hendrix, A. et al. Soluble cadherins as cancer biomarkers. Clin Exp Metastasis 24, 685–697 (2007). https://doi.org/10.1007/s10585-007-9104-8

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  • DOI: https://doi.org/10.1007/s10585-007-9104-8

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