Inhibition of Fibrinolysis, Associated with Oncogenic Transformation, by Normal and Antiplasmin-Depleted Human Plasma

When mixed cultures of mouse fibroblasts and mouse fibroblasts transformed with Kirsten murine sarcoma virus (Arch. ges .Virusforsch. 43, 345, 1973) were grown in petri dishes and overlayed with plasminogen-enriched casein, they showed foci of caseinolysis induced by plasminogen activator secreted by the transformed cells. Caseinolysis was inhibited by the addition of human plasma or bovine pancreatic trypsin inhibitor (BPTI) to the overlay, I ml of plasma being equivalent to 67 ± 18 (mean ± S.E.), kallikrein inhibitor (Kl) units of BPTI.

The culture fluid from a human melanoma line (gift of Dr. G. Barlow, Abbott Labs, III..), induced lysis of a fibrin clot, I ml of cuIture fluid being equivalent to 25 CTA units of urokinase . Fibrinolysis was inhibited by addition of human plasma or BPTI, I ml of plasma being equivalent to 94 ± 34 Kl units of BPTI.

Specific removal of antiplasmin, the fast-reacting plasmin inhibitor from plasma, by immuno-absorption, completely abolished its inhibitory activity on caseinolysis and on fibrinolysis. This depleted plasma still contained normal levels of the known plasma protease inhibitors. It is conduced that antiplasmin is the only protein in human plasma capable of inhibiting the fibrinolysis associated with oncogenic transformation or neoplasia. Whether this effect is exclusively due to inhibition of formed plasmin or also to interference with plasminogen activation remains unsettled.