Effect of Inhibitors of Fibrinolytic Enzymes on Development of Pulmonary Metastases

The administration of an inhibitor of fibrinolysis, ε-amino-caproic acid (EACA) or Bayer A128 (Trasylol), to rats just prior to the intravenous injection of 25,000 Walker 256 carcinosarcoma cells resulted in a significant increase in pulmonary metastases. The observed incidence of metastases in 100 animals each was: control, 33 percent; EACA, 20 mg, 39 percent; EACA, 40 mg, 85 percent; Bayer A128, 50 units, 43 percent; and Bayer A128, 75 units, 72 percent. These increases were not prevented by infusion of 7000 units of fibrinolysin. Heparin decreased the incidence, but the changes were not significant. When cancer cell counts were made, it was found that the blood of treated animals contained fewer cancer cells, and no cells were found after 30 minutes. When 1 ml of the blood from treated animals was injected subcutaneously into weanling rats, no tumor growth occurred. By contrast, blood from control animals induced tumor growth in a significant number of animals. These results seem to indicate that, with EACA and Bayer A128, the cancer cells are rapidly fixed in capillaries by fibrin or cell “stickiness” and cause an increase of metastases.