Publication
Novel interferon-lambdas induce antiproliferative effects in neuroendocrine tumor cells
Journal Paper/Review - Apr 24, 2006
Zitzmann Kathrin, Brand Stephan, Baehs Sebastian, Göke Burkhard, Meinecke Jennifer, Spöttl Gerald, Meyer Heinrich, Auernhammer Christoph J
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PubMed
Doi
Citation
Type
Journal
Publication Date
Issn Print
Pages
Brief description/objective
Interferon-alpha (IFN-alpha) is used for biotherapy of neuroendocrine carcinomas. The interferon-lambdas (IL-28A/B and IL-29) are a novel group of interferons. In this study, we investigated the effects of the IFN-lambdas IL-28A and IL-29 on human neuroendocrine BON1 tumor cells. Similar to IFN-alpha, incubation of BON1 cells with IL-28A (10 ng/ml) and IL-29 (10 ng/ml) induced phosphorylation of STAT1, STAT2, and STAT3, significantly decreased cell numbers in a proliferation assay, and induced apoptosis as demonstrated by poly(ADP-ribose) polymerase (PARP)-cleavage, caspase-3-cleavage, and DNA-fragmentation. Stable overexpression of suppressor of cytokine signaling proteins (SOCS1 and SOCS3) completely abolished the aforementioned effects indicating that SOCS proteins act as negative regulators of IFN-lambda signaling in BON1 cells. In conclusion, the novel IFN-lambdas IL-28A and IL-29 potently induce STAT signaling and antiproliferative effects in neuroendocrine BON1 tumor cells. Thus, IFN-lambdas may hint a promising new approach in the antiproliferative therapy of neuroendocrine tumors.