The The Role of Thrombomodulin in Prostate Tumor Cell Migration

Abstract

The Role of Thrombomodulin in Prostate Tumor Cell Migration Thrombomodulin (TM) is an endothelial transmembrane receptor that regulates coagulation by binding to thrombin and activating the protein C system. TM is also expressed by prostate cancer (CaP) cells. CaP associated TM activates the protein C system. We investigated if TM expressed by CaP cells may also be involved in tumor progression by determining its ability to regulate tumor cell migration. PC-3 and DU-145 CaP cell lines were incubated in a Boyden chamber in the presence and absence of monoclonal antibodies to each extracellular domain of TM and amount of cell migration determined. The extracellular domains of TM include an N-terminal lectin-like domain, six epidermal growth factor-like (EGF) domains, and a serine-threonine rich domain, which is differentially glycosylated with a chondroiten sulphate moiety. We determined that monoclonal antibodies to the chondroiten sulphate domain increased the ability of both PC-3 and DU-145 cell lines to migrate. We also investigated if CaP cell invasion was regulated by thrombin, protein C, and activated protein C. We determined that PC-3 and DU-145 cell migration was not regulated by these TM-associated proteins. We conclude that the chondroiten sulphate domain of CaP cell TM regulates cell migration. Funding Support: South Carolina NIH INBRE grant, Freedland Foundation, McKay Urology Endowment Fund