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Nicholl, Michael B.; Ledgewood, Chelsea L.; Chen, Xuhui; Bai, Qian; Qin, Chenglu; Cook, Kathryn M.; Herrick, Elizabeth J.; Diaz-Arias, Alberto; Moore, Bradley J.; Fang, Yujiang
Cytokine (Philadelphia, Pa.), 12/2014, Volume: 70, Issue: 2Journal Article
•IL-35 was found to be expressed mainly by epithelial derived PCAN cells in vivo.•IL-35 promoted growth and inhibited apoptosis in PCAN cell lines in vitro.•IL-35 might function as an autocrine growth factor in PCAN growth. Interleukin-35 (IL-35), an IL-12 cytokine family member, mediates the immune inhibitory function of regulatory T cells (Treg). We assayed the presence of IL-35 in paraffin-embedded human pancreas cancer (PCAN) and unexpectedly found IL-35 was expressed mainly by epithelial derived PCAN cells, but not by Treg. We further examined the expression and effect of exogenous IL-35 in human PCAN cell lines and found IL-35 promoted growth and inhibited apoptosis in PCAN cell lines. IL-35 induced proliferation correlated with an increase in cyclin B, cyclin D, cdk2, and cdk4 and a decrease in p27 expression, while inhibition of apoptosis was associated with an increase in Bcl-2 and a decrease in TRAILR1. We conclude IL-35 is produced by PCAN in vivo and promotes PCAN cell line growth in vitro. These results might indicate an important new role for IL-35 as an autocrine growth factor in PCAN growth.
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