Suppression of fibrinolysin T activity fails to restore density-dependent growth inhibition to SV3T3 cells

SMALL quantities of proteolytic enzymes added to cultures can cause untransformed fibroblastic cells to manifest transiently the altered growth potential 1,2 , enhanced lectin-mediated agglutinability 3 and enhanced glucose transport 4 characteristic of fibroblast cultures transformed by oncogenic viruses. Thus, the enhanced proteolytic activity of cells transformed by both oncogenic DNA viruses 5,6 and RNA viruses 7 may play an important role in the loss of density-dependent growth inhibition exhibited by virus-transformed cells. In particular, Reich et al. have shown that cells transformed by simian virus 40 (SV40) or Rous or murine sarcoma virus produce increased levels of a proteolytic activity (fibrinolysin T) which hydrolyses 125 I-fibrin 8,9 . This fibrinolysin T activity is the result of the conversion of serum plasminogen to plasmin by a plasminogen activator (cell factor) 10,11 . In addition, using plasminogendeficient serum prepared by affinity chromatography, Reich et al. have demonstrated plasminogen dependence of several phenotypic parameters associated with viral transformation 12 . We have used ε-aminocaproic acid (EACA), an inhibitor of plasminogen activation 13 and fibrinolysin T activity 8 , and found that suppression of the fibrinolysin T activity of SV40-transformed 3T3 (SV3T3) cell cultures does not restore density-dependent growth inhibition to these cells. This suggests that the enhanced plasmin level in SV3T3 cell cultures is not responsible for loss of density-dependent growth inhibition in this cell line.