title: IL-35 promotes pancreas cancer growth through enhancement of proliferation and inhibition of apoptosis: evidence for a role as an autocrine growth factor.
abstract: 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.
authors: Department of Surgery, University of Missouri School of Medicine, Columbia, MO 65212, USA; Ellis Fischel Cancer Center, University of Missouri School of Medicine, Columbia, MO 65212, USA. Electronic address: nichollm@health.missouri.edu.
authors: Michael B
authors: MB
authors: Nicholl
authors: Department of Surgery, University of Missouri School of Medicine, Columbia, MO 65212, USA.
authors: Chelsea L
authors: CL
authors: Ledgewood
authors: Department of Surgery, University of Missouri School of Medicine, Columbia, MO 65212, USA; Department of Surgery, Luohu Hospital, Shenzhen, China.
authors: Xuhui
authors: X
authors: Chen
authors: Department of Surgery, University of Missouri School of Medicine, Columbia, MO 65212, USA.
authors: Qian
authors: Q
authors: Bai
authors: Department of Surgery, University of Missouri School of Medicine, Columbia, MO 65212, USA; Department of Obstetrics & Gynecology, Luohu Hospital, Shenzhen, China.
authors: Chenglu
authors: C
authors: Qin
authors: Department of Surgery, University of Missouri School of Medicine, Columbia, MO 65212, USA.
authors: Kathryn M
authors: KM
authors: Cook
authors: Department of Surgery, University of Missouri School of Medicine, Columbia, MO 65212, USA.
authors: Elizabeth J
authors: EJ
authors: Herrick
authors: Department of Pathology, University of Missouri School of Medicine, Columbia MO 65212, USA.
authors: Alberto
authors: A
authors: Diaz-Arias
authors: Department of Surgery, University of Missouri School of Medicine, Columbia, MO 65212, USA.
authors: Bradley J
authors: BJ
authors: Moore
authors: Department of Microbiology & Immunology, Des Moines University College of Osteopathic Medicine, Des Moines, IA 50312, USA. Electronic address: yujiang.fang@dmu.edu.
authors: Yujiang
authors: Y
authors: Fang
mesh_terms: D057134:Antibodies, Neutralizing / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D019898:Autocrine Communication / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D007378:Interleukins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D018123:Receptors, Interleukin; C532417:interleukin-35, human
keywords: Apoptosis; IL-35; Pancreatic cancer; Proliferation