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 gammac chain-negative. We thus used these cell models to investigate the patterns of expression of IL13R alpha1, IL13R alpha2, and IL4R alpha chains and the role of IL13R alpha2 in the response to IL13. Using new specific antibodies and flow cytometry, we observed a similar surface expression of IL4R alpha and IL13R alpha1 chains in most RCC and glioma cells, whereas IL13R alpha2 was only present on five of six glioma cell lines. In all glioma cell lines, the amount of IL13R alpha2 expression was 10 to 30 times higher than that of the two other chains. Although there was no surface or intracellular expression of IL13R alpha2, its mRNA was detected in three of seven RCC cell lines. The expression on RCC cells of IL13R alpha2 mRNA and/or that of high-affinity IL13 binding sites is not sufficient to predict IL13R alpha2 protein expression. Blocking experiments showed that IL4 and IL13 strongly inhibited RCC cell proliferation through a unique receptor composed of IL4R alpha and IL13R alpha1 chains. Using RCC cells stably transfected with IL13R alpha2 cDNA, we showed that the overexpression of IL13R alpha2 decreased the response to IL13 but not that to IL4. Our results demonstrate that IL13R alpha2 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.