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Inhibition of autonomous human keratinocyte proliferation and amphiregulin mitogenic activity by sulfated polysaccharides

In Vitro Cellular & Developmental Biology - Animal volume 28, pages 218–222 (1992)Cite this article

Summary

We previously demonstrated that human keratinocyte cultures proliferate in the absence of polypeptide growth factors (autonomous growth) and that this autonomous growth is blocked by interaction of heparin with a human keratinocyte-derived autocrine factor (KAF) which we identified as amphiregulin (AR). In the present study, we demonstrate that sulfated polysaccharides other than heparin (low and high molecular weight dextran sulfates) also inhibit the AR-mediated autonomous proliferation of human keratinocytes. Furthermore, sulfated polysaccharides such as high and low molecular weight dextran sulfates, heparan sulfate and, to a lesser extent, chondroitin sulfates B and C were also shown to be inhibitors of human keratinocyte-derived AR (k-d AR)-stimulated DNA synthesis in quiescent murine AKR-2B cell cultures. Our results demonstrate that sulfation of polysaccharides is required for AR inhibitory activity, and that several sulfated polysaccharides (other than heparin) can act as inhibitors of AR-mediated autonomous proliferation in human epidermal keratinocytes and as inhibitors of k-d AR-mediated mitogenic activity in AKR-2B cells.

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Affiliations

  1. The Department of Cell Biology and Anatomy, The Oregon Health Sciences University, 97201, Portland, Oregon

    Paul W. Cook, Paul A. Mattox, Winifred W. Keeble & Gary D. Shipley

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  1. Paul W. Cook
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  2. Paul A. Mattox
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  3. Winifred W. Keeble
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  4. Gary D. Shipley
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Cook, P.W., Mattox, P.A., Keeble, W.W. et al. Inhibition of autonomous human keratinocyte proliferation and amphiregulin mitogenic activity by sulfated polysaccharides. In Vitro Cell Dev Biol - Animal 28, 218–222 (1992). https://doi.org/10.1007/BF02631096

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  • DOI: https://doi.org/10.1007/BF02631096

Key words

  • amphiregulin
  • heparin
  • sulfated polysaccharide
  • human keratinocyte