Thrombomodulin modulates cell migration in human melanoma cell lines

Thrombomodulin modulates cell migration in human melanoma cell lines

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,...

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Bibliographic Details
Published in:Melanoma research Vol. 24; no. 1; pp. 11 - 19
Main Authors: de Oliveira, Andreia da Silva, Yang, Likiu, Echevarria-Lima, Juliana, Monteiro, Robson Q, Rezaie, Alireza R
Format: Journal Article
Language:English
Published: England 01-02-2014
Subjects:
Adenomatous Polyposis Coli Protein - pharmacology
Antigens, CD - biosynthesis
Cell Line, Tumor
Cell Movement - physiology
Disease Progression
Down-Regulation
Endothelial Protein C Receptor
Humans
Interleukin-8 - biosynthesis
Melanocytes - metabolism
Melanocytes - pathology
Melanoma - genetics
Melanoma - metabolism
Melanoma - pathology
Neoplasm Invasiveness
Receptors, Cell Surface - biosynthesis
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
Thrombin - pharmacology
Thrombomodulin - genetics
Thrombomodulin - metabolism
Thromboplastin - biosynthesis
Transfection
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Summary: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.
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ISSN:0960-8931
1473-5636
DOI:10.1097/CMR.0000000000000035