Abstract
Thrombomodulin (TM) is a receptor for thrombin, and best known for its role as a cofactor in an anticoagulant pathway. TM is distributed on the plasma membrane of vascular endothelial cells and in circulating plasma as soluble form. We demonstrated previously that soluble form of TM (sTM) reduced invasion activity of murine melanoma cells in vitro and the injection of sTM suppressed experimental lung metastasis of the cells in mice. Many studies describe that several proteins involved in fibrinolytic pathway plays a critical role in tumor cell invasion. Thrombin-activable fibrinolysis inhibitor (TAFI) is a plasma zymogen that is activated by thrombin. Activated TAFI prevents fibrinolysis by removing C-terminal lysine residues from fibrin. Thrombin-medeated activation of plasma TAFI is greatly enhanced in the presence of the TM. Therefore, TM is not only anticoagulant factor but also a cofactor for antifibrinolytic pathway in the thrombin dependent cascade. Here we investigated the involvement of TAFI and TM in the regulation of cancer cell invasion. The invasion activity was significantly inhibited in human fibrosarcoma HT1080 cells that had been transfected with TM expression vector in the presence of plasma as compared to that with empty vector. The invasion activity of HT1080 cells was partially enhanced by addition of TAFI inhibitor. These findings indicate the possibility that TM expression on cell surface is involved in the inhibition of tumor cell invasion at least in part through plasma TAFI activation. The possible role of TAFI and TM in cancer cell invasion will be further discussed. [J Physiol Sci. 2007;57 Suppl:S60]
