title: RAGE and S100 protein transcription levels are highly variable in human melanoma tumors and cells.
abstract: The Receptor for Advanced Glycation Endproducts (RAGE) has been suggested to play an important role in melanoma. Animal studies with anti-RAGE antibodies have shown that RAGE blockade leads to reduced melanoma tumor growth and metastasis formation. RAGE is a multiligand receptor and among its ligands are the Ca-binding S100 proteins. Certain S100 proteins are differentially expressed in melanoma. For example, S100B is currently used as a reliable prognostic biomarker in patients with malignant melanoma. We have surveyed 40 human melanoma tumor samples for the transcription of RAGE and five of its known S100 protein ligands. Compared to normal skin tissue, we found highly significant (p < 0.0001) over-expression of S100B and underexpression of S100A2, whereas no significant difference in transcription of S100A6 and S100A10 was observed. RAGE showed slightly increased transcription in stage IV. Between individual tumor samples tremendous differences in transcription of the S100 proteins were observed, whereas RAGE expression showed relatively little variance. We also analyzed three well-characterized melanoma cell lines for S100 and RAGE expression. The S100 protein transcription profile showed clear differences between cultured melanoma cells and melanoma tumor tissue. Detailed profiling of S100 and RAGE transcription in melanoma tumors in combination with imunohisto-chemical and clinical data may lead to improved molecular diagnostic of melanoma and subsequently may facilitate improved treatment in the future.
authors.affiliation: Department of Pharmaceutical Sciences, NDSU, Fargo, ND 58108-6950, USA. Estelle.Leclerc@ndsu.edu
authors.forename: Estelle
authors.initials: E
authors.lastname: Leclerc
authors.forename: Claus W
authors.initials: CW
authors.lastname: Heizmann
authors.forename: Stefan W
authors.initials: SW
authors.lastname: Vetter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017306:Annexin A2 / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002630:Chemotactic Factors / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008024:Ligands; D008297:Male; D008545:Melanoma / Q000378:metabolism*; D008875:Middle Aged; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins / Q000378:metabolism*; D014158:Transcription, Genetic; D000099248:S100 Calcium Binding Protein A10
chemical_list: D017306:Annexin A2; D018797:Cell Cycle Proteins; D002630:Chemotactic Factors; D008024:Ligands; D000067759:Receptor for Advanced Glycation End Products; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins; D000099248:S100 Calcium Binding Protein A10; C098997:S100A2 protein, human; C055351:S100A6 protein, human