IL-13Rα2 is a Glioma-Restricted Receptor for Interleukin-13

Abstract

We have found that binding sites for interleukin-13. ( IL13) are overexpressed in a vast majority of high-grade astrocytomas. (HGAs). These binding sites for IL-13 are distinct from the physiological receptor in that it does not bind IL-4. We also demonstrated that IL-13 receptor alpha 2 protein chain. (IL-13Rα2), an IL-4-independent receptor for IL-13, is abundant among HGAs, but not in normal organs. To examine if IL-13Rα2 is the tumorassociated site for IL-13, we stably transfected normal Chinese hamster ovary. (CHO) cells and glioma G-26 cells to express either human. (h) or murine. (m) IL13Rα2. CHO-hlL-13Rα2(+) cells and G-26-hlmlL13Rα2(+) cells, not CHO and G-26 parental or mock -transfected cells, specifically bound IL-13 in an IL-4-independent manner. The IL-13Rα2(+) cells also became highly susceptible to the killing by an IL-13-based cytotoxic fusion protein. In loss of function studies, a HGA cell line, SNB-19, was transfected with antisense. (as) hIL-13Rα2, as-SNB-19-hIL-13Rα2(+) cells lost their natural affinity towards IL-13 and became resistant to IL-13-based cytotoxins. The fact, that IL13Rα2-positive cells bind IL-13 independent of IL-4, become susceptible to IL-13 cytotoxins, cells deprived of IL-13Rα2 receptor lose these features, demonstrates that IL-13Rα2 is the brain tumor-associated receptor for IL-13.

Keywords

• main tumors
• gliomas
• cymtoxin
• receptor
• interleukin-13
• cyokine