Loss of Interleukin-13-Receptor-Alpha-1 Induces Apoptosis and Promotes EMT in Pancreatic Cancer |
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Authors: | Jingwei Shi Xiao Shen Qi Kang Xing Yang Maximilian Denzinger Marko Kornmann Benno Traub |
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Affiliation: | Department of General and Visceral Surgery, Ulm Univsersity Hospital, Albert-Einstein-Allee 23, 89081 Ulm, Germany; (J.S.); (X.S.); (Q.K.); (X.Y.); (M.D.); (M.K.) |
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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. |
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Keywords: | interleukin 4 interleukin 13 interleukin-13-receptor-alpha-1 cytokines EMT pancreatic cancer progression |
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