title: RAGE overexpression confers a metastatic phenotype to the WM115 human primary melanoma cell line.
abstract: The formation of melanoma metastases from primary tumor cells is a complex phenomenon that involves the regulation of multiple genes. We have previously shown that the receptor for advanced glycation end products (RAGE) was up-regulated in late metastatic stages of melanoma patient samples and we hypothesized that up-regulation of RAGE in cells forming a primary melanoma tumor could contribute to the metastatic switch of these cells. To test our hypothesis, we overexpressed RAGE in the WM115 human melanoma cell line that was established from a primary melanoma tumor of a patient. We show here that overexpression of RAGE in these cells is associated with mesenchymal-like morphologies of the cells. These cells demonstrate higher migration abilities and reduced proliferation properties, suggesting that the cells have switched to a metastatic phenotype. At the molecular level, we show that RAGE overexpression is associated with the up-regulation of the RAGE ligand S100B and the down-regulation of p53, ERK1/2, cyclin E and NF-kB. Our study supports a role of RAGE in the metastatic switch of melanoma cells.
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, PO Box 6050, Fargo, ND 58108-6050, USA.
authors.forename: Varsha
authors.initials: V
authors.lastname: Meghnani
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, PO Box 6050, Fargo, ND 58108-6050, USA.
authors.forename: Stefan W
authors.initials: SW
authors.lastname: Vetter
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, PO Box 6050, Fargo, ND 58108-6050, USA. Electronic address: Estelle.Leclerc@ndsu.edu.
authors.forename: Estelle
authors.initials: E
authors.lastname: Leclerc
mesh_terms: D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D019927:Cyclin E / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016328:NF-kappa B / Q000235:genetics; D009362:Neoplasm Metastasis; D010641:Phenotype; D000067759:Receptor for Advanced Glycation End Products / Q000096:biosynthesis* / Q000235:genetics; D064568:S100 Calcium Binding Protein beta Subunit / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D019927:Cyclin E; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D064568:S100 Calcium Binding Protein beta Subunit; C579160:S100B protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Melanoma; Metastatic switch; RAGE; S100B; p53 cancer