title: Thrombomodulin modulates cell migration in human melanoma cell lines.
abstract: Malignant melanoma cells are known to have altered expressions of growth factors as compared with normal melanocytes. Thrombomodulin (TM) is a thrombin receptor on endothelial cells that converts thrombin from a procoagulant to an anticoagulant enzyme. TM expression is downregulated in tumor cells, and this phenomenon correlates with tumor cell invasiveness and a poor prognosis in patients with cancer. In this study, we evaluated TM expression in two human melanoma cell lines that are known to have either low (WM35) or high (A375) aggressive phenotypes. Analysis by quantitative real-time PCR (qPCR) showed that the mRNA expression of TM is modestly (WM35) or dramatically (A375) downregulated in melanoma cells, as compared with human primary melanocytes. TM expression levels inversely correlated with in-vitro migration properties of tumor cells. In addition, interleukin-8 expression also correlated with the degree of aggressiveness, as indicated by high expression levels of this cytokine in A375 cells. Overexpression of TM in A375 cells by transient transfection reversed their aggressive phenotype and dramatically decreased interleukin-8 expression by these cells. Taken together, these results suggest that downregulation of TM plays a crucial role in melanocyte transformation and melanoma progression.
authors.affiliation: aInstitute of Medical Biochemistry bPaulo Goés Microbiology Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil cEdward A. Doisy Department of Biochemistry and Molecular Biology, St Louis University School of Medicine, St Louis, Missouri, USA.
authors.forename: Andreia da Silva
authors.initials: Ada S
authors.lastname: de Oliveira
authors.forename: Likiu
authors.initials: L
authors.lastname: Yang
authors.forename: Juliana
authors.initials: J
authors.lastname: Echevarria-Lima
authors.forename: Robson Q
authors.initials: RQ
authors.lastname: Monteiro
authors.forename: Alireza R
authors.initials: AR
authors.lastname: Rezaie
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D018450:Disease Progression; D015536:Down-Regulation; D000074283:Endothelial Protein C Receptor; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D008544:Melanocytes / Q000378:metabolism / Q000473:pathology; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D013917:Thrombin / Q000494:pharmacology; D018180:Thrombomodulin / Q000235:genetics / Q000378:metabolism*; D013925:Thromboplastin / Q000096:biosynthesis; D014162:Transfection
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D015703:Antigens, CD; D000074283:Endothelial Protein C Receptor; D016209:Interleukin-8; C478370:PROCR protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018180:Thrombomodulin; D013925:Thromboplastin; D013917:Thrombin