Abstract PO-092: Influence of the IL-13-receptor alpha 1 chain on the malignant phenotype of pancreatic cancer cells

Abstract

Abstract Introduction: Increasing evidence indicates salient activities of Interleukin (IL)-4, IL-13 and their specific Type-II-IL-4 receptor complex (IL-4Rα/IL-13Rα1) in carcinomas including pancreatic cancer. While IL-4 seems to be tumor-promoting in PDAC, the specific role of the IL-13/IL-13Rα1 axis was yet to be determined. Both cytokines are abundant in PDAC through cells of the tumor microenvironment. In this project, we planned to determine the specific effects of the IL-13Rα1-receptor chain on the malignant phenotype of pancreatic cancer cells. Methods: Expression of IL-13Rα1, IL-4Rα, and the human common gamma chain (γc) in cultured pancreatic cancer cell lines AsPC-1, Capan-1, PANC-1, MIA PaCa-2 and A818-6 as well as downstream signal transduction factors of IL13-Rα1 were detected by Western blot. The role of IL-13Rα1 in pancreatic cancer cell proliferation, mobility and migration was demonstrated based on the successful establishment of stable shRNA based IL-13Rα1-knockdown (KD) clones in Capan-1 and MIA PaCa-2 cell lines. Results: Not only the basal anchorage-dependent growth but also the anchorage-independent growth in soft agar were inhibited in Capan-1 and MIA PaCa-2 cells due to IL-13Rα1-downregulation. Mechanistically, IL-13Rα1-KD was associated with increased apoptosis. Additionally, signal transduction factors STAT3, STAT6, PI3K, Akt and ERK1/2 were activated in Capan-1 exposed to exogenous IL-4 and IL-13. Interestingly, IL-13Rα1-KD reduced the basal expression of STAT3, Akt and ERK1/2. IL-4 and IL-13 induced activation of STAT3, ERK1/2, Akt and STAT6 was significantly suppressed in Capan-1-IL-13Rα1-KD (C-KD) clones. Furthermore, IL-13Rα1-KD resulted in enhanced mobility and migration in Capan-1 cells. Conclusion: It was demonstrated that endogenous IL-13Rα1 is vital for pancreatic cancer cell growth with the involvement of STAT3/6, ERK1/2 and Akt. Surprisingly, IL-13Rα1-KD resulted in enhanced mobility and migration. Overall, IL-13Rα1 plays a critical but heterogenous role in PDAC. Our findings increase the understanding of the different functions and mechanisms involving IL-13Rα1 in pancreatic cancer progression. Citation Format: Jingwei Shi, Marko Kornmann, Benno Traub. Influence of the IL-13-receptor alpha 1 chain on the malignant phenotype of pancreatic cancer cells [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-092.