Receptor for Advanced Glycation End Products (RAGE) as a Novel Target for Inhibiting Breast Cancer Bone Metastasis

Abstract

Abstract : Receptor for advanced glycation end products (RAGE) expression has been shown to be detected in human cancers, including 63% of breast carcinomas. RAGE has been shown to play an important role in inflammation and cancer. RAGE also regulates trafficking of myeloid-derived suppressor cells, which have been shown to suppress anti-tumorigenic responses. Furthermore, RAGE has also been shown to play an important role in insulin resistance and diabetes, which is linked to breast cancer progression and metastasis. Our hypothesis is that targeting RAGE plays an important role in breast cancer metastasis, especially to bone. S100A7, which plays an important role in breast cancer progression and metastasis, was recently shown to bind to RAGE. We analyzed S100A7/RAGE-mediated effects on osteoclast formation. We also analyzed the role of RAGE on tumor growth using RAGE knockout mouse models, as well as in mS100a7a15 (murine ortholog of human S100A7) transgenic mouse models. We also analyzed the role of RAGE in regulating breast cancer chemotaxis, chemoinvasion, and wound healing in vitro.