title: The receptor for advanced glycation end products influences the expression of its S100 protein ligands in melanoma tumors.
abstract: Recent studies have suggested that the receptor for advanced glycation end products (RAGE) participates in melanoma progression by promoting tumor growth. However, the mechanisms of RAGE activation in melanoma tumors are not clearly understood. To get deeper insights into these mechanisms, we transfected a melanoma cell line, which was established from a human melanoma primary tumor, with RAGE, and studied the effect of RAGE overexpression on cell proliferation and migration in vitro. We observed that overexpression of RAGE in these cells not only resulted in significantly increased migration rates compared to control cells, but also in decreased proliferation rates (Meghnani et al., 2014). In the present study, we compared the growth of xenograft tumors established from RAGE overexpressing WM115 cells, to that of control cells. We observed that when implanted in mice, RAGE overexpressing cells generated tumors faster than control cells. Analysis of protein tumor extracts showed increased levels of the RAGE ligands S100B, S100A2, S100A4, S100A6 and S100A10 in RAGE overexpressing tumors compared to control tumors. We show that the tumor growth was significantly reduced when the mice were treated with anti-RAGE antibodies, suggesting that RAGE, and probably several S100 proteins, were involved in tumor growth. We further demonstrate that the anti-RAGE antibody treatment significantly enhanced the efficacy of the alkylating drug dacarbazine in reducing the growth rate of RAGE overexpressing tumors.
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, Dept. 2665, PO BOX 6050, Fargo, ND 58108, United States.
authors.forename: Varsha
authors.initials: V
authors.lastname: Meghnani
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, Dept. 2665, PO BOX 6050, Fargo, ND 58108, United States.
authors.forename: Anil
authors.initials: A
authors.lastname: Wagh
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, Dept. 2665, PO BOX 6050, Fargo, ND 58108, United States.
authors.forename: Venkata S K
authors.initials: VS
authors.lastname: Indurthi
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, Dept. 2665, PO BOX 6050, Fargo, ND 58108, United States.
authors.forename: Mohit
authors.initials: M
authors.lastname: Koladia
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, Dept. 2665, PO BOX 6050, Fargo, ND 58108, United States.
authors.forename: Stefan W
authors.initials: SW
authors.lastname: Vetter
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, Dept. 2665, PO BOX 6050, Fargo, ND 58108, United States.
authors.forename: Benedict
authors.initials: B
authors.lastname: Law
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, Dept. 2665, PO BOX 6050, Fargo, ND 58108, United States. Electronic address: Estelle.Leclerc@ndsu.edu.
authors.forename: Estelle
authors.initials: E
authors.lastname: Leclerc
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D003606:Dacarbazine / Q000494:pharmacology; D005260:Female; D006801:Humans; D008024:Ligands; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D011897:Random Allocation; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D009418:S100 Proteins / Q000096:biosynthesis*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D008024:Ligands; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009418:S100 Proteins; D003606:Dacarbazine
keywords: Antibody therapy; Dacarbazine; Melanoma; RAGE; S100B