Loss of Interleukin-13-Receptor-Alpha-1 Induces Apoptosis and Promotes EMT in Pancreatic Cancer

Int J Mol Sci. 2022 Mar 26;23(7):3659. doi: 10.3390/ijms23073659.

Abstract

In search of new therapies for pancreatic cancer, cytokine pathways have attracted increasing interest in recent years. Cytokines play a vital role in the crosstalk between tumour cells and the tumour microenvironment. The related inflammatory cytokines IL-4 and IL-13 can regularly be detected at increased levels in the microenvironment of pancreatic cancer. They share a receptor heterodimer consisting of IL-4Rα and IL-13Rα1. While IL-4Rα induces a more oncogenic phenotype, the role of IL-13Rα1 was yet to be determined. ShRNA-based knockdown of IL-13Rα1 was performed in Capan-1 and MIA PaCa-2. We assessed cell growth and migratory capacities under the influence of IL-13Rα1. Pathway alterations were detected by immunoblot analysis. We now have demonstrated that the loss of IL-13Rα1 induces apoptosis in pancreatic cancer cells. This was associated with an epithelial-to-mesenchymal transition. Loss of IL-13Rα1 also abolished the effects of exogenous IL-4 and IL-13 stimulation. Interestingly, in wild type cells, cytokine stimulation caused a similar increase in migratory capacities as after IL-13Rα1 knockdown. Overall, our results indicate the vital role of IL-13Rα1 in the progression of pancreatic cancer. The differential expression of IL-4Rα and IL-13Rα1 has to be taken into account when considering a cytokine-targeted therapy in pancreatic cancer.

Keywords: EMT; cytokines; interleukin 13; interleukin 4; interleukin-13-receptor-alpha-1; pancreatic cancer progression.

MeSH terms

  • Apoptosis
  • Cytokines / metabolism
  • Humans
  • Interleukin-13 Receptor alpha1 Subunit / genetics
  • Interleukin-13* / pharmacology
  • Interleukin-4 / metabolism
  • Interleukin-4 / pharmacology
  • Pancreatic Neoplasms* / genetics
  • Tumor Microenvironment

Substances

  • Cytokines
  • IL13RA1 protein, human
  • Interleukin-13
  • Interleukin-13 Receptor alpha1 Subunit
  • Interleukin-4