Role of urokinase-type plasminogen activator and inhibitory effect of protease inhibitor in invasion and metastasis of pancreatic cancer.

We investigated the association of urokinase-type plasminogen activator (u-PA) with tumor cell invasion and hepatic metastasis using human pancreatic cancer cell lines (SW1990, PANC-1, and RWP-1). We also examined the effect of the protease inhibitor, gabexate mesilate. SW1990 cells showed a higher u-PA activity (41.2 U/ml) in substrate assay and invasiveness (21.6% IV) than PANC-1 (14.3 U/ml, 10.3% IV) and RWP-1 (22.1, 13.5), which correlated with in vivo hepatic metastasis. Gabexate mesilate significantly reduced the u-PA activity, invasiveness, and hepatic metastasis of SW1990 cells. These findings suggest the possible application of protease inhibitors to prevent tumor invasion and metastasis.