RAGE signaling inhibition prevents the malignant transformation of pancreatic ductal adenocarcinoma cells

Abstract Background Receptor for advanced glycation end-products (RAGE) is implicated in immune and inflammatory diseases as well as the malignant transformation 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 transformation of pancreatic ductal adenocarcinoma (PDAC). Methods Four PDAC cell lines were used. Quantitative real-time reverse transcription PCR (qRT-PCR) 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. Results 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. Conclusions inhRAGE inhibits the malignant transformation of PDAC, suggesting that inhRAGE may be a novel therapeutic agent for the condition.