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

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-4R alpha and IL-13R alpha 1. While IL-4R alpha induces a more oncogenic phenotype, the role of IL-13R alpha 1 was yet to be determined. ShRNA-based knockdown of IL-13R alpha 1 was performed in Capan-1 and MIA PaCa-2. We assessed cell growth and migratory capacities under the influence of IL-13R alpha 1. Pathway alterations were detected by immunoblot analysis. We now have demonstrated that the loss of IL-13R alpha 1 induces apoptosis in pancreatic cancer cells. This was associated with an epithelial-to-mesenchymal transition. Loss of IL-13R alpha 1 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-13R alpha 1 knockdown. Overall, our results indicate the vital role of IL-13R alpha 1 in the progression of pancreatic cancer. The differential expression of IL-4R alpha and IL-13R alpha 1 has to be taken into account when considering a cytokine-targeted therapy in pancreatic cancer.

Automated summary

In the search for new pancreatic cancer therapies, cytokine pathways have gained increasing interest. Inflammatory cytokines IL-4 and IL-13 are often found at increased levels in the microenvironment of pancreatic cancer. Loss of IL-13R alpha 1 induces apoptosis and epithelial-to-mesenchymal transition in pancreatic cancer cells. The differential expression of IL-4R alpha and IL-13R alpha 1 should be considered when targeting cytokine therapy in pancreatic cancer.