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Open Access Highly Accessed Review

RAGE (Receptor for Advanced Glycation Endproducts), RAGE Ligands, and their role in Cancer and Inflammation

Louis J Sparvero1, Denise Asafu-Adjei2, Rui Kang3, Daolin Tang3, Neilay Amin4, Jaehyun Im5, Ronnye Rutledge5, Brenda Lin5, Andrew A Amoscato6, Herbert J Zeh3 and Michael T Lotze3*

Author Affiliations

1 Department of Surgery, University of Pittsburgh Cancer Institute, Pittsburgh, USA

2 Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, USA

3 Departments of Surgery and Bioengineering, University of Pittsburgh Cancer Institute, Pittsburgh, USA

4 University of Pennsylvania, Philadelphia, USA

5 Harvard University, Cambridge, USA

6 Departments of Surgery, Bioengineering, and Pathology, University of Pittsburgh Cancer Institute, Pittsburgh, USA

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Journal of Translational Medicine 2009, 7:17  doi:10.1186/1479-5876-7-17

Published: 17 March 2009

Abstract

The Receptor for Advanced Glycation Endproducts [RAGE] is an evolutionarily recent member of the immunoglobulin super-family, encoded in the Class III region of the major histocompatability complex. RAGE is highly expressed only in the lung at readily measurable levels but increases quickly at sites of inflammation, largely on inflammatory and epithelial cells. It is found either as a membrane-bound or soluble protein that is markedly upregulated by stress in epithelial cells, thereby regulating their metabolism and enhancing their central barrier functionality. Activation and upregulation of RAGE by its ligands leads to enhanced survival. Perpetual signaling through RAGE-induced survival pathways in the setting of limited nutrients or oxygenation results in enhanced autophagy, diminished apoptosis, and (with ATP depletion) necrosis. This results in chronic inflammation and in many instances is the setting in which epithelial malignancies arise. RAGE and its isoforms sit in a pivotal role, regulating metabolism, inflammation, and epithelial survival in the setting of stress. Understanding the molecular structure and function of it and its ligands in the setting of inflammation is critically important in understanding the role of this receptor in tumor biology.