Overexpression of tissue factor pathway inhibitor-2 (TFPI-2), decreases the invasiveness of prostate cancer cells in vitro

Human tissue factor pathway inhibitor-2 (TFPI-2) is a 32-kDa serine proteas e inhibitor that inhibits plasmin, trypsin, chymotrypsin, cathepsin G, and plasma kallikrein but not urokinase and tissue-type plasminogen activators or thrombin. After discovering that TFPI-2 expression is downregulated or l ost during tumor progression, we investigated the role of TFPI-2 in the inv asiveness of the prostate cancer cell line (LNCaP). We stably transfected L NCaP cells with a 0.7-kb vector expressing TFPI-2 in the sense orientation and measured the expression of TFPI-2 protein and mRNA by these cells by We stern and Northern blotting. Neither TFPI-2 protein nor mRNA was expressed by parental LNCaP cells or vector-transfected controls, but levels of both protein and mRNA were significantly increased in the sense-TFPI-2 clones. T he sense clones were less invasive than the control cells in Matrigel invas ion and spheroid migration assays. This is the first demonstration that upr egulation of TFPI-2 plays a significant role in the invasive behavior of hu man prostate cancer cells.