Abstract A37: The role of IL-6 in the interaction between fibroblasts and tumor cells in esophageal adenocarcinoma

Often described as wounds that do not heal, cancer cells depend on interactions with the surrounding stroma to develop and progress. Among the various stromal components, cancer-associated fibroblasts (CAFs) play a critical role in promoting tumor growth and invasion, leading to treatment resistance and poor survival in a number of cancers, including esophageal adenocarcinoma. Mechanistically, CAFs communicate with tumor cells in large part via secreted signaling factors. One such factor, interleukin-6 (IL-6), has been shown to be secreted by CAFs to promote angiogenesis, epithelial-to-mesenchymal transition (EMT), tumor cell stemness, and treatment resistance in adenocarcinomas of the colon, pancreas, stomach, and breast. In EAC, the upregulation of IL-6 signaling among tumor cells, particularly as a result of exposure to reflux, is well characterized. However, the role of IL-6 as a potential mediator of the CAF-tumor cell interaction in EAC remains poorly understood.To confirm that IL-6 is indeed involved in this interaction, we used ELISA to study the dynamics of IL-6 secretion by activated fibroblasts (FEF3303, FEF3 and PDF.G.P) and EAC cells (OE-19 and OE-33) in the setting of mono- and co-culture. We found that the interaction of CAFs and EAC cells in co-culture dramatically increased IL-6 levels compared to either EAC cells or fibroblasts alone. Next, we considered the relevance of these findings to human disease by examining human EAC biopsy specimens for patterns of ...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Cell-Cell Signaling in the Tumor Microenvironment Source Type: research