Influence of type-I Interferon receptor expression level on the response to type-I Interferons in human pancreatic cancer cells

Authors

  • Stephanie Booy,

    1. Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, Rotterdam, The Netherland
    2. Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands
    Search for more papers by this author
  • Casper H. J. van Eijck,

    1. Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands
    Search for more papers by this author
  • Fadime Dogan,

    1. Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, Rotterdam, The Netherland
    Search for more papers by this author
  • Peter M. van Koetsveld,

    1. Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, Rotterdam, The Netherland
    Search for more papers by this author
  • Leo J. Hofland

    Corresponding author
    1. Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, Rotterdam, The Netherland
    • Correspondence to: Leo J. HOFLAND,

      Department of Internal Medicine, Division of Endocrinology,

      Erasmus Medical Center Rotterdam, Dr. Molewaterplein 50,

      Rotterdam 3015 GE, The Netherlands.

      Tel.: +31 10 7034633

      Fax: +31 10 7035430

      E-mail: l.hofland@erasmusmc.nl

    Search for more papers by this author

Abstract

Pancreatic cancer is a highly aggressive malignancy with limited treatment options. Type-I interferons (e.g. IFN-α/-β) have several anti-tumour activities. Over the past few years, clinical studies evaluating the effect of adjuvant IFN-α therapy in pancreatic cancer yielded equivocal results. Although IFN-α and -β act via the type-I IFN receptor, the role of the number of receptors present on tumour cells is still unknown. Therefore, this study associated, for the first time, in a large panel of pancreatic cancer cell lines the effects of IFN-α/-β with the expression of type-I IFN receptors. The anti-tumour effects of IFN-α or IFN-β on cell proliferation and apoptosis were evaluated in 11 human pancreatic cell lines. Type-I IFN receptor expression was determined on both the mRNA and protein level. After 7 days of incubation, IFN-α significantly reduced cell growth in eight cell lines by 5–67%. IFN-β inhibited cell growth statistically significant in all cell lines by 43–100%. After 3 days of treatment, IFN-β induced significantly more apoptosis than IFN-α. The cell lines variably expressed the type-I IFN receptor. The maximal inhibitory effect of IFN-α was positively correlated with the IFNAR-1 mRNA (P < 0.05, r = 0.63), IFNAR-2c mRNA (P < 0.05, r = 0.69) and protein expression (P < 0.05, r = 0.65). Human pancreatic cancer cell lines variably respond to IFN-α and -β. The expression level of the type-I IFN receptor is of predictive value for the direct anti-tumour effects of IFN-α treatment. More importantly, IFN-β induces anti-tumour effects already at much lower concentrations, is less dependent on interferon receptor expression and seems, therefore, more promising than IFN-α.

Ancillary