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

Pancreatic cancer is a highly aggressive malignancy with limited treatment options. Type-I interferons (e.g. IFN-/-) have several anti-tumour activities. Over the past few years, clinical studies evaluating the effect of adjuvant IFN- therapy in pancreatic cancer yielded equivocal results. Although IFN- and - 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-/- with the expression of type-I IFN receptors. The anti-tumour effects of IFN- or IFN- 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 7days of incubation, IFN- significantly reduced cell growth in eight cell lines by 5-67%. IFN- inhibited cell growth statistically significant in all cell lines by 43-100%. After 3days of treatment, IFN- induced significantly more apoptosis than IFN-. The cell lines variably expressed the type-I IFN receptor. The maximal inhibitory effect of IFN- 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- and -. The expression level of the type-I IFN receptor is of predictive value for the direct anti-tumour effects of IFN- treatment. More importantly, IFN- induces anti-tumour effects already at much lower concentrations, is less dependent on interferon receptor expression and seems, therefore, more promising than IFN-.