1 Department of Anatomy, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 33302, Taiwan
Abstract Text: Interleukin (IL)-13, an immunoregulatory cytokine produced by various immune cells, is known to inhibit the production of inflammatory cytokines. Its receptor, IL13RA2, lacks an intracellular kinase domain, despite serving as a high-affinity membrane receptor for IL-13. Initially considered a decoy receptor to prevent excessive IL-13 signaling, IL13RA2 has been found to be overexpressed in numerous human tumors. However, its specific roles and functions can vary based on the cellular context. The functions of IL13RA2 in the human prostate remain largely unexplored. Thus, our study investigates the expression, functions, and regulatory mechanisms of IL13RA2 in prostate-associated cells. In silico analysis of TCGA data reveals downregulation of IL13RA2 in prostate cancers, and low expression of IL13RA2 correlates with poor overall survival. Furthermore, overexpression of IL13RA2 inhibits proliferation, migration, invasion, and suppresses AKT and ERK phosphorylation in prostate cancer cells in vitro. Xenograft animal studies demonstrate that IL13RA2 overexpression inhibits angiogenesis and reduces tumor growth in vivo. Notably, treatment with TGF-β or TNF-α downregulates IL13RA2 expression in human prostate fibroblasts (HPrF) cells in vitro. Our findings suggest that IL13RA2, identified as a tumor suppressor gene, plays significant roles in tumor progression and may serve as a potential therapeutic target for prostate cancer.
