Data from A Novel Role of Interleukin-13 Receptor α2 in Pancreatic Cancer Invasion and Metastasis

Abstract

<div>Abstract<p>Whereas interleukin-13 receptor α2 chain (IL-13Rα2) is overexpressed in a variety of human solid cancers including pancreatic cancer, we investigated its significance in cancer invasion and metastasis. We used two pancreatic cancer cell lines, <i>IL-13Rα2</i>–negative HPAF-II and <i>IL-13Rα2</i>–positive HS766T, and generated <i>IL-13Rα2</i> stably transfected HPAF-II as well as <i>IL-13Rα2</i> RNA interference knocked-down HS766T cells. Ability of invasion and signal transduction was compared between <i>IL-13Rα2</i>–negative and <i>IL-13Rα2</i>–positive cells and tumor metastasis was assessed in murine model for human pancreatic cancer with orthotopic implantation of tumors. IL-13 treatment enhanced cell invasion in <i>IL-13Rα2</i>–positive cancer cell lines but not in <i>IL-13Rα2</i>–negative cell lines. Furthermore, gene transfer of <i>IL-13Rα2</i> in negative cell lines enhanced invasion, whereas its silencing downmodulated invasion of pancreatic cell lines in a Matrigel invasion assay. <i>In vivo</i> study revealed that <i>IL-13Rα2</i>–positive cancer metastasized to lymph nodes, liver, and peritoneum at a significantly higher rate compared with <i>IL-13Rα2</i>–negative tumors. The expression of <i>IL-13Rα2</i> in metastatic lesions was found to be increased compared with primary tumors, and mice with <i>IL-13Rα2</i>–positive cancer displayed cachexia and poor prognosis. Invasion and metastasis also correlated with increased matrix metalloproteinase protease activity in these cells. Mechanistically, IL-13 activated extracellular signal-regulated kinase 1/2 and activator protein-1 nuclear factors in <i>IL-13Rα2</i>–positive pancreatic cancer cell lines but not in <i>IL-13Rα2</i>–negative cell lines. Taken together, our results show for the first time that IL-13 can signal through IL-13Rα2 in pancreatic cancer cells and <i>IL-13Rα2</i> may serve as a prognostic biomarker of invasion and metastasis in pancreatic cancer. [Cancer Res 2009;69(22):8678–85]</p></div>