RAGE signaling inhibition prevents the malignant phenotypes of pancreatic ductal adenocarcinoma cells.

Receptor for advanced glycation end-products (RAGE) is implicated in immune and inflammatory diseases as well as the malignant phenotypes of cancer. Blocking RAGE signaling is thought to reduce its impact on disease states. In this study, we investigated the effect of RAGE signaling inhibitors (inhRAGE) on the malignant phenotypes of pancreatic ductal adenocarcinoma (PDAC). Four PDAC cell lines were used. quantitative PCR (qPCR) was performed to evaluate RAGE expression. Assays for cell proliferation, migration, and invasion were performed with or without inhRAGE and the addition of several ligands. The effects of inhRAGE were examined by creating ectopic and orthotopic xenograft tumor models, and the resected specimens were subjected to immunohistochemical analysis. RAGE expression was confirmed in all the cell lines. inhRAGE significantly reduced the migration and invasion abilities of the cells exposed to high-mobility group B1 (HMGB1) or S100B, which are tumor- and inflammation-associated RAGE ligands, without inhibiting cellular proliferation. In both the ectopic and orthotopic models, inhRAGE treatment significantly inhibited tumor growth. Immunostaining confirmed the suppression of angiogenesis and inflammation. inhRAGE inhibits the malignant phenotypes of PDAC, suggesting that inhRAGE may be a novel therapeutic agent for the condition.