The role of interleukin-6 classic and trans-signaling and interleukin-11 classic signaling in gastric cancer cells

Introduction: The cytokine interleukin-11 (IL-11) binds on its target cells to a membrane-bound IL-11R, which results in homodimerization of the signal-transducing (3-receptor gp130. Recent studies have uncovered a pro- inflammatory role in several diseases, including different tumor entities, and mouse models have revealed a crucial role of the IL-11/IL-11R axis in gastric cancer. However, studies regarding human gastric cancer are sparse, and whether the results obtained in mouse models also hold true in the human situation is little investigated. Material and methods: We analyzed gene expression of IL11RA, , IL11, , IL6R, , IL6 and IL6ST in different gastric tumor and immune cell lines. Furthermore, we stimulated these cell lines with exogenous cytokines and determined intracellular signaling. Finally, we analyzed gene expression data of gastric tumor patients and correlated them with overall patient survival. Results: This study showed that different gastric tumor cell lines respond to IL-6 classic and trans-signaling, but only slightly to stimulation with IL-11. We observed that monocyte-like cell lines expressed high levels of IL-6R and responded to IL-6, but not to stimulation with IL-11. Using gene expression data, we found that IL11RA and IL11 are not overexpressed in human gastric cancer tissue and do not correlate with patient survival. However, low IL6 expression is associated with higher overall survival. Conclusions: We provided evidence for IL-6 but not IL-11 signaling in gastric tumor cells and demonstrated that IL6 expression in gastric tumors is associated with overall survival of patients.