Role of Protease-activated Receptor 1 in Tumor Metastasis Promoted by Tissue Factor

Michael E. Bromberg; Michelle A. Bailly; William H. Konigsberg

doi:10.1055/s-0037-1616053

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2001; 86(05): 1210-1214
DOI: 10.1055/s-0037-1616053

Review Article

Schattauer GmbH

Role of Protease-activated Receptor 1 in Tumor Metastasis Promoted by Tissue Factor

Michael E. Bromberg

¹Yale University School of Medicine, Department of Internal Medicine, New Haven, CT, USA

,

Michelle A. Bailly

¹Yale University School of Medicine, Department of Internal Medicine, New Haven, CT, USA

,

William H. Konigsberg

²Yale University, Department of Molecular Biophysics and Biochemistry, New Haven, CT, USA

› Author Affiliations

Abstract

Summary

Tissue factor (TF) is a transmembrane glycoprotein that complexes with factor VIIa to initiate blood coagulation. We previously reported that expression of high levels of TF in a human melanoma cell line promotes metastasis. Both the cytoplasmic domain of TF and its extracellular domain complexed with factor VIIa are required for the meta-static effect. To further explore the mechanism of TF-mediated metastasis, we investigated the possibility that a protease-activated receptor (PAR) might play a role. For this purpose, we first determined the expression levels of the known PARs (PAR1-4) in a human melanoma cell line, SIT1, that has low endogenous levels of TF and low meta-static potential. We found negligible levels of all of the known PARs and transfection of this cell line with human TF cDNA did not alter expression of the known PARs. To study the possible role of PAR1 in TF-mediated metastasis, we prepared a panel of transfected cell lines with varying levels of TF and PAR1. Our studies show that TF promotes metastasis by a pathway that does not involve high expression of known PARs by tumor cells. In addition, while overexpression of PAR1 is insufficient to induce metastasis in cells with low TF expression, it enhances the metastatic potential of cells with high TF expression, indicating a possible synergy between TF and PAR1 in promoting metastasis.

Keywords

Tissue factor - protease-activated receptor - factor VIIa - metastasis - melanoma

Full Text

References

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