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

Abstract

SMALL quantities of proteolytic enzymes added to cultures can cause untransformed fibroblastic cells to manifest transiently the altered growth potential1,2, enhanced lectin-mediated agglutinability3 and enhanced glucose transport4 characteristic of fibroblast cultures transformed by oncogenic viruses. Thus, the enhanced proteolytic activity of cells transformed by both oncogenic DNA viruses5,6 and RNA viruses7 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 125I-fibrin8,9. 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 transformation12. We have used e-aminocaproic acid (EACA), an inhibitor of plasminogen activation13 and fibrinolysin T activity8, 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.