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-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.
Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, Rotterdam, The Netherland; Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands.
Stephanie
S
Booy
Casper H J
CH
van Eijck
Fadime
F
Dogan
Peter M
PM
van Koetsveld
Leo J
LJ
Hofland
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D000077190:Interferon alpha-2; D000068556:Interferon beta-1a; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
C507964:IFNAR1 protein, human; C508033:IFNAR2 protein, human; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012333:RNA, Messenger; D011994:Recombinant Proteins; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta; D000068556:Interferon beta-1a
IFNAR-1; IFNAR-2c; Type-I interferons; anti-cancer effects; pancreatic cancer