IL-35 promotes pancreas cancer growth through enhancement of proliferation and inhibition of apoptosis: evidence for a role as an autocrine growth factor

Cytokine. 2014 Dec;70(2):126-33. doi: 10.1016/j.cyto.2014.06.020. Epub 2014 Jul 26.

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.

Keywords: Apoptosis; IL-35; Pancreatic cancer; Proliferation.

MeSH terms

  • Antibodies, Neutralizing / pharmacology
  • Apoptosis* / drug effects
  • Apoptosis* / genetics
  • Autocrine Communication* / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Humans
  • Interleukins / genetics
  • Interleukins / metabolism*
  • Neoplasm Proteins / metabolism
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin / metabolism

Substances

  • Antibodies, Neutralizing
  • Interleukins
  • Neoplasm Proteins
  • RNA, Messenger
  • Receptors, Interleukin
  • interleukin-35, human