Department of General and Visceral Surgery, Ulm Univsersity Hospital, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
Int J Mol Sci. 2022 Mar 26;23(7):3659. doi: 10.3390/ijms23073659.
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.
为了寻找胰腺癌的新疗法，近年来细胞因子途径引起了越来越多的关注。细胞因子在肿瘤细胞与肿瘤微环境的相互作用中起着至关重要的作用。相关的炎症细胞因子 IL-4 和 IL-13 通常可以在胰腺癌的微环境中检测到水平升高。它们共享由 IL-4Rα 和 IL-13Rα1 组成的受体异二聚体。虽然 IL-4Rα 诱导更致癌的表型，但 IL-13Rα1 的作用尚未确定。在 Capan-1 和 MIA PaCa-2 中，通过 shRNA 敲低 IL-13Rα1。我们评估了在 IL-13Rα1 影响下的细胞生长和迁移能力。通过免疫印迹分析检测通路改变。我们现在已经证明，IL-13Rα1 的缺失会诱导胰腺癌细胞凋亡。这与上皮间质转化有关。IL-13Rα1 的缺失也消除了外源性 IL-4 和 IL-13 刺激的作用。有趣的是，在野生型细胞中，细胞因子刺激引起的迁移能力增加与 IL-13Rα1 敲低后相似。总的来说，我们的结果表明 IL-13Rα1 在胰腺癌的进展中起着至关重要的作用。在考虑针对胰腺癌的细胞因子靶向治疗时，必须考虑到 IL-4Rα 和 IL-13Rα1 的差异表达。
