Novel interferon-lambdas induce antiproliferative effects in neuroendocrine tumor cells.
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.
Zitzmann
Kathrin
K
Department of Internal Medicine II, University-Hospital Munich-Grosshadern, University of Munich, Munich, Germany.
Brand
Stephan
S
Baehs
Sebastian
S
Göke
Burkhard
B
Meinecke
Jennifer
J
Spöttl
Gerald
G
Meyer
Heinrich
H
Auernhammer
Christoph J
CJ
D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology / Q000627:therapeutic use*; D053938:DNA Fragmentation; D006801:Humans; D007372:Interferons / Q000494:pharmacology / Q000627:therapeutic use*; D007378:Interleukins / Q000494:pharmacology / Q000627:therapeutic use*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000378:metabolism; D010766:Phosphorylation; D011065:Poly(ADP-ribose) Polymerases; D018121:Receptors, Cytokine / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D053701:Receptors, Interleukin-10; D012097:Repressor Proteins / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D000095022:Interferon Lambda
D053148:Caspase 3; D020169:Caspases; D016207:Cytokines; D007372:Interferons; D007378:Interleukins; D047908:Intracellular Signaling Peptides and Proteins; D011065:Poly(ADP-ribose) Polymerases; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D012097:Repressor Proteins; D050791:STAT Transcription Factors; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C108944:SOCS1 protein, human; C106644:SOCS3 protein, human; C471046:interleukin 28alpha receptor; C505407:CASP3 protein, human