Suppression of pulmonary metastases of rat mammary cancer by recombinant urokinase plasminogen activator inhibitor.

A pivotal point in the process of invasion and metastasis of cancer cells rests on the capability of those cells to present a proteolytic interface to the surrounding tissue matrix as well as to the lymphovascular channels supplying the tumor. The MATB rat mammary cancer cells used in this study, along with a number of cancers of epithelial cell origin, provide that proteolytic interface by cell surface-bound plasmin. Inhibition of tumor cell surface plasmin formation in this study was achieved through the addition of the urokinase plasminogen activator inhibitor (PAI-2) to the infusion of rat mammary cancer cells introduced into the pulmonary arterial circulation of female Fisher 344 rats. The results show a significant decrease in the numbers of pulmonary metastases in those rats receiving the inhibitor. This effect was demonstrable for cells delivered as a bolus as well as for those delivered slowly over a 7-day period via an osmotic pump. Delivery of the inhibitor was by osmotic pump in each instance. The evidence suggests a basis for an additional approach to control the spread of selected cancers.