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Thrombomodulin modulates cell migration in human melanoma cell lines

de Oliveira, Andreia da Silvaa; Yang, Likiuc; Echevarria-Lima, Julianab; Monteiro, Robson Q.a; Rezaie, Alireza R.c

doi: 10.1097/CMR.0000000000000035

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.

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

Correspondence to Alireza R. Rezaie, PhD, Edward A. Doisy Department of Biochemistry and Molecular Biology, St Louis University School of Medicine, 1100 S. Grand Blvd., St Louis, MO 63104, USA Tel: +1 314 977 9240; fax: +1 314 977 9205; e-mail:

Received March 6, 2013

Accepted October 17, 2013

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins