Several proteins bind RAGE, such as S100a4 and high-mobility group-binding proteins (HMGB)18,20–22, which play a pivotal role in tumor microenvironment-mediated metastatic progression18,20,21; however, whether tumor cells produce extracellular S100a4 or other RAGE ligands and the mechanisms of function remains to be investigated. The gene discussed is S100A4; the disease is neoplasm.