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.
Evans
D M
DM
Department of Surgery, Akron General Medical Center, OH 44307, USA.
Lin
P L
PL
D000818:Animals; D005260:Female; D005341:Fibrinolysin / Q000037:antagonists & inhibitors; D007260:Infusion Pumps; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary*; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D009375:Neoplasms, Glandular and Epithelial / Q000473:pathology / Q000517:prevention & control / Q000556:secondary; D017396:Plasminogen Activator Inhibitor 2 / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors*
D017396:Plasminogen Activator Inhibitor 2; D011994:Recombinant Proteins; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator