(271 KB) - Supplementary Figure S1. Expression of IL4R� and IL13R�1 in KM12 cells. Supplementary Figure S2. IL-13 quantification in conditioned medium of KM12 cells. Supplementary Figure S3. IL13R�1 is not involved in cell migration and invasion in response to IL-13. Supplementary Figure S4. Overexpression of IL13R�2 increases cell migration and invasion in response to IL-13.
ARTICLE ABSTRACT
Autocrine secretion of cytokines by metastatic colorectal cancer cells and their role during invasion and liver homing has been poorly characterized. In this study, we used cytokine arrays to analyze the secretomes of poorly and highly metastatic colorectal cancer cells. Compared with poorly metastatic cancer cells, highly metastatic cells expressed increased levels of the immunosuppressive cytokines interleukin (IL)-4 and IL-13 in addition to increased surface expression of the high affinity IL-13 receptor IL-13Rα2, suggesting that IL-13Rα2 mediates IL-13 effects in colorectal cancer cells. Silencing of IL-13Rα2 in highly metastatic cells led to a decrease in adhesion capacity in vitro and a reduction in liver homing and increased survival in vivo, revealing a role for this receptor in cell adhesion, migration, invasion, and metastatic colonization. In support of this, IL-13 signaling activated the oncogenic signaling molecules phosphoinositide 3-kinase, AKT, and SRC in highly metastatic cells. Clinically, high expression of IL-13Rα2 was associated with later stages of disease progression and poor outcome in patients with colorectal cancer. Our findings therefore support a critical role for IL-13Rα2 expression in colon cancer invasion and metastasis. Cancer Res; 72(11); 2780–90. ©2012 AACR.
