Protein S attenuates the invasive potential of THP-1 cells by interfering with plasminogen binding on cell surface via a protein C-independent mechanism.

Protein S, a cofactor for activated protein C (aPC) to inactivate coagulation factors, also plays a pivotal role in inflammation. Based on our recent findings that aPC and protein S modifies tissue plasminogen activator (tPA)-catalyzed activation of Glu-plasminogen (Glu-plg), we analyzed possible role of protein S in cell-associated plasminogen activation and invasive potential of inflammatory cells. Monocyte-like THP-1 cells, to which both plasminogen and tPA bind, enhanced tPA-catalyzed plasminogen activation, which was partially abolished by protein S but not by aPC. Protein S attenuated both the plasminogen binding to THP-1 cells and associated their invasive potential through Matrigel.