Expression of interleukin 13 receptor in glioma and renal cell carcinoma: IL13Rα2 as a decoy receptor for IL13

Glioma and renal cell carcinoma (RCC) cells express high affinity interleukin 13 (IL13) binding sites, but only RCC cell proliferation was inhibited by IL13. Both of these two cell types are IL2-receptor γc chain-negative. We thus used these cell models to investigate the patterns of expression of IL13Rα1, IL13Rα2, and IL4Rα chains and the role of IL13Rα2 in the response to IL13. Using new specific antibodies and flow cytometry, we observed a similar surface expression of IL4Rα and IL13Rα1 chains in most RCC and glioma cells, whereas IL13Rα2 was only present on five of six glioma cell lines. In all glioma cell lines, the amount of IL13Rα2 expression was 10 to 30 times higher than that of the two other chains. Although there was no surface or intracellular expression of IL13Rα2, its mRNA was detected in three of seven RCC cell lines. The expression on RCC cells of IL13Rα2 mRNA and/or that of high-affinity IL13 binding sites is not sufficient to predict IL13Rα2 protein expression. Blocking experiments showed that IL4 and IL13 strongly inhibited RCC cell proliferation through a unique receptor composed of IL4Rα and IL13Rα1 chains. Using RCC cells stably transfected with IL13Rα2 cDNA, we showed that the overexpression of IL13Rα2 decreased the response to IL13 but not that to IL4. Our results demonstrate that IL13Bα2 acts as a decoy receptor for IL13 and that it may exert a tight regulation of IL13 activity without impairing the IL4 response of the same cell target.