Inhibitory role of plasminogen activator inhibitor-1 in invasion and proliferation of HLE hepatocellular carcinoma cells

Plasminogen activator inhibitor (PAI)-1, a serine protease inhibitor, inact ivates urokinase-type plasminogen activator (uPA) and regulates degradation of the extracellular matrix; whether it functions for or against tumor pro gression, however, has been the subject of controversy. To assess the role of PAI-1 in invasion and proliferation of hepatocellular carcinoma (HCC) ce lls, HLE cells were transfected with a vector capable of expressing an anti sense PAI-1 transcript, Analysis of seven stably transfected clones (PAI-1( -)) showed reductions of 81% in PAI-1 mRNA by northern blot analysis and 63 % in the cellular PAI-1 antigen level by enzyme-linked immunosorbent assay (ELISA), There was no change in the levels of secreted PAI-1 or PAI-2, The activity of cellular uPA increased by 54%, without change in the protein le vel or the secreted uPA activity evaluated by ELISA, Morphologically, PAI-1 antisense induced a spindle shape with narrower cytoplasmic processes in H LE cells. The forced inhibition of PAI-1 increased the invasion and the gro wth of PAI-1(-) cells by 75% and 82%, respectively. These results suggest t hat PAI-1 plays a role in inhibiting invasion and proliferation, and the ba lance between uPA and PAI-1 expression is important to assess the invasiven ess of HCC cells.