In vivo overexpression of IL-13 receptor α2 chain inhibits tumorigenicity of human breast and pancreatic tumors in immunodeficient mice

Interleukin 13 receptor alpha2 (IL-13R alpha2) chain is highly expressed on some tumor cell lines and primary cell cultures. This receptor chain plays an important role in ligand binding and internalization. To determine the functional significance of overexpression of this chain, we stably transfected IL-13R alpha2 chain in human breast (MDA-MB-231) and pancreatic (PANC-1) cancer cell lines that naturally do not express this chain. There was no difference in growth between vector only transfected and IL-13R alpha2 chain transfected cells in vitro. However, surprisingly, in immunodeficient mice, tumorigenicity was profoundly inhibited in IL-13R alpha2 chain overexpressing tumors. Because breast tumors that grew later showed loss of IL-13R alpha2 gene expression, lack of tumorigenicity correlated positively with IL-13R alpha2 chain expression. Inflammatory cells including neutrophils and macrophages were identified in IL-13R alpha2 overexpressing regressing tumors and neutrophils were found to produce IL-13. IL-13 showed a modest antitumor activity to IL-13R alpha2 chain overexpressing tumors in vitro and in vivo. Furthermore, IL-13Ra2 chain overexpressing tumors constitutively produced IL-8 that has been shown to have antitumor effect. These results establish a novel function of a cytokine receptor chain and further suggest that the presence of this chain on tumor cells by itself may play a key role in tumorigenicity.