Modulation of heparan-sulphate/chondroitin-sulphate ratio by glycosaminoglycan biosynthesis inhibitors affects liver metastatic potential of tumor cells

Authors

  • József Tímár,

    Corresponding author
    1. First Institute of Pathology and Experimental Cancer Research, Semmelweis University of Medicine, Budapest, VIII. Üllöi Ú t 26, H-1085 Hungary
    • First Institute of Pathology and Experimental Cancer Research, Semmelweis University of Medicine, Budapest, VIII. Üllöi Ú t 26, H-1085 Hungary Fax: (36)-1–1–335–784
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  • Csaba Diczházi,

    1. Department of Molecular Pathology, Joint Research Organization of the Hungarian Academy of Sciences and the Semmelweis University of Medicine, Budapest, Hungary
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  • Irén Bartha,

    1. Department of Molecular Pathology, Joint Research Organization of the Hungarian Academy of Sciences and the Semmelweis University of Medicine, Budapest, Hungary
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  • Gábor Pogány,

    1. Department of Molecular Pathology, Joint Research Organization of the Hungarian Academy of Sciences and the Semmelweis University of Medicine, Budapest, Hungary
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  • SÁNdor Paku,

    1. Department of Molecular Pathology, Joint Research Organization of the Hungarian Academy of Sciences and the Semmelweis University of Medicine, Budapest, Hungary
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  • Erzsébet Rásó,

    1. First Institute of Pathology and Experimental Cancer Research, Semmelweis University of Medicine, Budapest, VIII. Üllöi Ú t 26, H-1085 Hungary
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  • József Tóvári,

    1. First Institute of Pathology and Experimental Cancer Research, Semmelweis University of Medicine, Budapest, VIII. Üllöi Ú t 26, H-1085 Hungary
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  • Andrea Ladányi,

    1. Department of Molecular Pathology, Joint Research Organization of the Hungarian Academy of Sciences and the Semmelweis University of Medicine, Budapest, Hungary
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  • Károly Lapis,

    1. Department of Molecular Pathology, Joint Research Organization of the Hungarian Academy of Sciences and the Semmelweis University of Medicine, Budapest, Hungary
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  • László Kopper,

    1. First Institute of Pathology and Experimental Cancer Research, Semmelweis University of Medicine, Budapest, VIII. Üllöi Ú t 26, H-1085 Hungary
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  • András Jeney

    1. First Institute of Pathology and Experimental Cancer Research, Semmelweis University of Medicine, Budapest, VIII. Üllöi Ú t 26, H-1085 Hungary
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Abstract

Previous data have indicated that the proteoglycan (PG) pattern is different on tumor cells with different liver metastatic potential. We selected “conventional” glycosaminoglycan (GAG) biosynthesis inhibitors, β T-D-xyloside (BX), 2-deoxy-D-glucose (2-DG), ethane-1-hydroxy-1, 1-diphosphonate (ETDP) and the newly discovered 5-hexyl-2-deoxyuridine (HUdR), to modulate PGs on highly metastatic/liver-specific 3LL-HH murine carcinoma and HT168 human melanoma cells and to influence their liver colonization potential. These compounds all induced remarkable changes in GAG biosynthesis, but to varying degrees: glucosamine labelling was affected mainly by 2-DG, and HUdR and sulphation by BX and HUdR. Furthermore, the ratio of he paran sulphate/chondroitin sulphate (HS/CS) of PGs was increased by ETDP and decreased after treatment by HUdR. In addition to changes in PG metabolism, tumor-cell proliferation and adhesion to fibronectin were affected; BX and 2-DG stimulated cell proliferation and adhesion, while HUdR inhibited both proliferation and adhesion. Most interestingly, HUdR, the most effective inhibitor of HS/HSPG, depressed the formation of liver colonies, while ETDP, the most effective inhibitor of CS/CSPG, stimulated the appearance of liver colonies. These observations indicated that, at least in these experimental systems, tumor cells with a high HS/CS ratio are more likely to form liver metastases; consequently, anti-HS agents could also be anti-metastatic. © 1995 Wiley-Liss, Inc.

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