Abstract 2422: Epithelial interleukin-4 receptor promotes metastasis of mammary tumor cells

Abstract

Abstract Interleukin-4 (IL4) is known primarily for its immune system functions where it can stimulate lymphocytes and promote macrophage activation. Various cancer cells, including breast, are now known to express functionally active IL4 receptors, which appear to play a role in cell survival. We believe that blocking IL4 signaling specifically in epithelial cells will attenuate metastasis because of reduced cell survival in secondary sites. To test this hypothesis, we have generated multiple clones of two murine mammary tumor cell lines that show efficient knockdown of an essential component of the IL4 receptor, IL4-receptor [IL4R] alpha. Initial characterization of knockdown and control clones showed a significantly slower growth rate in vitro as assessed both by metabolic (MTT) assays and direct cell counting. Flow cytometric analysis using either annexin V staining or sub G1 measurement showed that clones lacking IL4Ralpha had 2-fold higher basal levels of apoptosis. To test effects in vivo, we have performed experimental and spontaneous metastasis assays using clones of the 4T1 cell line. Both pulmonary and hepatic metastatic lesions were significantly decreased [2.4-fold lower] in mice injected with IL4Ralpha knockdown clones compared to controls. There was however no significant effect on the primary mammary tumors. Together these results suggest that IL4 signaling in epithelial tumor cells is pro-metastatic, and blocking it may be a useful therapeutic approach for preventing metastatic spread. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2422. doi:10.1158/1538-7445.AM2011-2422