Human primary colon carcinomas xenografted into nude mice. I. Characterization of plasminogen activators expressed by primary tumors and their xenografts.

Analysis was made of plasminogen activator (PA) activities present in 0.125% Triton X-100 extracts of human primary colon carcinomas and of their respective serial subcutaneous xenografts in nude mice. A correlation between tumor invasiveness and PA expression was observed in that primary tumors exhibiting clearly invasive growth patterns demonstrated high concentrations of PAs while subcutaneous xenografts, exhibiting noninvasive pseudobenign growth, contained very low levels of PA activity. The decrease in fibrinolytic activity observed in subcutaneous xenografts was not due to an increase in inhibitors of fibrinolytic activity. Immunologic characterization of PAs in tumor extracts showed that over 90% of human PA activity was of the urokinase type. Furthermore, tumor-derived urokinase was shown to be present in a proenzyme form. It was resistant to diisopropyl fluorophosphate (DFP) and was not inhibited by purified PA inhibitor. However, after its activation into urokinase by plasmin, it was completely inhibited by DFP and PA inhibitor.