CHARACTERIZATION OF PROTEASE EXPRESSION IN HUMAN PROSTATE-CANCER CELL-LINES

To better understand the biochemical mechanisms necessary for prostate cancer invasion and metastases, we studied the expression and interac tion of proteolytic enzymes cathepsin D, cathepsin B, urokinase and co llagenase IV in human prostate cell lines LNCAP (hormone sensitive) an d DU145 (hormone refractory). Cellular fractionation and immunoblottin g revealed that both cell lines expressed similar amounts of the 34 kD form of cathepsin D, 72 kD form of collagenase IV and the 55 kD form of urokinase. However, DU145 expressed an increased amount of the 28 k D form of cathepsin B. When E64, a cysteine protease inhibitor was add ed, a decreased amount of the active cathepsin D was expressed. Furthe rmore, when cathepsin B was added to concentrated plasma membrane homo genates, urokinase was processed to its active form at 33 kD. E64 inhi bited the ability of both cell lines to degrade fibronectin. An in vit ro Boyden chamber demonstrated that DU145 was more motile than LNCAP a nd that preincubation with E64 could decrease motility of both cell li nes. We suggest that cathepsin B may promote tumor invasion not only b y proteolysis of basement membrane components, but also by activating other proteases.