Endogenously Expressed IL-4Rα Promotes the Malignant Phenotype of Human Pancreatic Cancer In Vitro and In Vivo

Int J Mol Sci. 2017 Mar 28;18(4):716. doi: 10.3390/ijms18040716.


Exogenous interleukin-4 (IL-4) has been demonstrated to affect the growth of different human malignancies including pancreatic cancer cells. The aim of our study was to determine the role of endogenously expressed IL-4-receptor-α-chain (IL-4Rα) in pancreatic cancer cells. IL-4Rα-suppression was achieved by generating Capan-1 cells stably expressing shRNA targeting IL-4Rα. The malignant phenotype was characterized by assessing growth properties, directional and non-directional cell movement in vitro and tumor growth in vivo. Signaling pathways were analyzed upon IL-4 and IL-13 stimulation of wildtype (WT) and control-transfected cells compared to IL-4Rα-knockdown cells. Silencing of IL-4Rα resulted in reduced anchorage-dependent cell growth (p < 0.05) and reduced anchorage-independent colony size (p < 0.001) in vitro. Moreover, cell movement and migration was inhibited. IL-4 and IL-13 stimulation of Capan-1-WT cells induced activation of similar pathways like stimulation with Insulin-like growth factor (IGF)-I. This activation was reduced after IL-4Rα downregulation while IGF-I signaling seemed to be enhanced in knockdown-clones. Importantly, IL-4Rα silencing also significantly suppressed tumor growth in vivo. The present study indicates that endogenously expressed IL-4 and IL-4Rα contribute to the malignant phenotype of pancreatic cancer cells by activating diverse pro-oncogenic signaling pathways. Addressing these pathways may contribute to the treatment of the disease.

Keywords: IL-13-receptor-α1-chain; IL-4-receptor-α-chain; interleukin-4; interleukin-4-receptor; pancreatic cancer.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Genetic Predisposition to Disease
  • Humans
  • In Vitro Techniques
  • Interleukin-3 / metabolism
  • Interleukin-4 / metabolism*
  • Interleukin-4 Receptor alpha Subunit / antagonists & inhibitors
  • Interleukin-4 Receptor alpha Subunit / genetics*
  • Mice
  • Neoplasm Transplantation
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology*
  • RNA, Small Interfering / pharmacology*
  • Signal Transduction


  • IL3 protein, human
  • IL4 protein, human
  • IL4R protein, human
  • Interleukin-3
  • Interleukin-4 Receptor alpha Subunit
  • RNA, Small Interfering
  • Interleukin-4