Human ovarian-carcinoma cell lines express IL-4 and IL-13 receptors: Comparison between IL-4- and IL-13-induced signal transduction

Abstract

We have reported that human ovarian-carcinoma cell lines express high-affinity IL-4 receptor. Since IL-4R has been hypothesized to share a chain with IL-13R, we investigated whether ovarian cancer cells express IL-13 receptor. In the present study, we report that the ovarian-carcinoma cell lines IGROV-1 and PA-1 express varying numbers of high-affinity IL-13 receptors. Furthermore, IL-13 inhibited the binding of IL-4 on both ovarian-carcinoma cell lines, while IL-4 did not inhibit IL-13 binding on IGROV-1 cell line. IL-13 and IL-4 induced the phosphorylation of JAK1, JAK2 and Tyk2 Janus kinases in PA-1 cells. In contrast, JAK3 tyrosine kinase was expressed in PA-1 cells, but IL-4 or IL-13 did not augment its phosphorylation. In IGROV-1 cells, Tyk2 was constitutively phosphorylated and this phosphorylation was augmented by IL-4 or IL-13. JAK1 and JAK2 but not JAK3 were expressed but only JAK2 was faintly phosphorylated in response to either IL-13 or IL-4 respectively. IRS (insulin-receptor substrate)-1 and IRS-2 were also phosphorylated constitutively in both ovarian cancer cell lines examined, but only the phosphorylation of IRS-1 was augmented in response to IL-4 or IL-13. STAT6 was phosphorylated and activated in response to IL-4 and IL-13 in all cell lines examined. Our results demonstrate that ovarian cancer cell lines may express 2 types of IL-13R and the IL-13- or IL-4-induced signaling patterns may be slightly different in each type of receptor.