UC San Diego

Pancreatic cancer patients have a five-year survival rate of approximately 6%, far worse than any other common malignancy. Clearly a greater understanding of the multiple signaling pathways involved in pancreatic cancer progression is needed to develop more effective treatment for this devastating disease. Interleukin-11 (IL-11) is a member of the IL-6 class of cytokines and has been implicated in the development and/or progression of multiple human cancers. IL-11 promotes inflammation involved in tumor progression, cell migration and proliferation, differentiation of tumor cells in the tumor microenvironment, invasiveness, and survival. However, the role of IL-11 in pancreatic cancer is largely unknown. In this study, we show that the IL-11 ligand is overexpressed in pancreatic cancer. In cultured pancreatic cancer cells, IL-11 signaling activates the Akt, ERK, and Stat3 signaling pathways, yet IL-11 has no effect on cell proliferation or migration. We demonstrate that TGF-[Beta] increases IL-11 expression by pancreatic cancer associated fibroblasts (CAFs), an effect mediated by the ERK signaling pathway. Our results thus far show IL-11 activates core oncogenic signaling pathways in pancreatic cancer cells and thus IL-11 signaling may help promote pancreatic cancer progression. Further studies are necessary to better define the oncogenic phenotypes impacted by IL-11 in the pancreatic cancer microenvironment