Regulation of human melanoma growth and metastasis by AGE-AGE receptor interactions.

Abstract

Advanced glycation end products (AGE), nonenzymatically glycated protein derivatives, have been implicated in the development and progression of diabetic angiopathies, including skin dermopathy. Nevertheless, the involvement of AGE in the development and progression of melanoma has not been fully elucidated. In this study we investigated the expression levels of their receptor for AGE (RAGE) in human melanoma and subsequently studied the effects of AGE on melanoma growth and migration. First, RAGE was detected in the cytoplasm of human melanoma cells (G361 and A375). Among the different types of AGE, glyceraldehyde- and glycolaldehyde-derived AGE significantly stimulated the growth and migration of human melanoma cells. Furthermore, tumor formation of melanoma cell xenografts in athymic mice was prevented by treatment with anti-RAGE neutralizing antibodies. In tumor-bearing mice, survival rates were prolonged, and spontaneous pulmonary metastases were inhibited by treatment using anti-RAGE neutralizing antibodies. In addition, all AGE were present in beds of human melanoma tumor, whereas they were barely detected in normal skin. These results suggest that AGE might be involved in the growth and invasion of melanoma through interactions with RAGE and represent promising candidates for assessing the future therapeutic potential of this therapy in treating patients with melanoma.

• Authors: Riichiro Abe, Tadamichi Shimizu, Hiroshi Sugawara, Hirokazu Watanabe, Hideki Nakamura, Hiroshi Choei, Nobuyuki Sasaki, Sho-ichi Yamagishi, Masayoshi Takeuchi, Hiroshi Shimizu
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 122 Issue 2 Pg. 461-7 (Feb 2004) ISSN: 0022-202X [Print] United States
• PMID: 15009731 (Publication Type: Journal Article)

Chemical References

• Antibodies
• Glycation End Products, Advanced
• Receptor for Advanced Glycation End Products
• Receptors, Immunologic

Topics

• Animals
• Antibodies (pharmacology)
• Cell Division (physiology)
• Cell Movement (physiology)
• Gene Expression Regulation, Neoplastic
• Glycation End Products, Advanced (metabolism)
• Humans
• Immunocompetence
• In Vitro Techniques
• Lung Neoplasms (metabolism, mortality, secondary)
• Melanoma (metabolism, mortality, secondary)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Transplantation
• Receptor for Advanced Glycation End Products
• Receptors, Immunologic (immunology, metabolism)
• Skin Neoplasms (metabolism, mortality, pathology)