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[Cancer Research 62, 4805-4811, August 15, 2002]
© 2002 American Association for Cancer Research

Tumor Biology

Receptor for Advanced Glycation End Products-binding COOH-terminal Motif of Amphoterin Inhibits Invasive Migration and Metastasis1

Henri J. Huttunen2, Carole Fages, Juha Kuja-Panula, Anne J. Ridley and Heikki Rauvala

Program of Molecular Neurobiology, Institute of Biotechnology, and Department of Biosciences, University of Helsinki, Helsinki FIN-00014, Finland [H. J. H., J. K-P., H. R.], and Ludwig Institute for Cancer Research, Royal Free and University College School of Medicine, London W1W 7BS, United Kingdom [C. F., A. J. R.]

Amphoterin has been suggested to regulate invasive process extension and cell migration in tumor cells and embryonic neurons through binding to receptor for advanced glycation end products (RAGE), a multiligand transmembrane receptor belonging to the immunoglobulin superfamily. In this study, we identify a COOH-terminal motif in amphoterin (amino acids 150–183) that is responsible for RAGE binding. We show that as a surface-bound ligand, this part of amphoterin is sufficient to induce RAGE-dependent process extension, suggesting a role in the regulation of cell motility. When applied in solution, the RAGE-binding COOH-terminal motif of amphoterin efficiently inhibits process extension and transendothelial migration of tumor cells. Furthermore, in an in vivo model, the corresponding synthetic peptide significantly suppresses formation of lung metastases. Taken together, these results suggest that amphoterin binds to RAGE through a COOH-terminal motif that can be used as an efficient inhibitor to block invasive migration of tumor cells.




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Copyright © 2002 by the American Association for Cancer Research.