Y. Morita et al., Inhibitory role of plasminogen activator inhibitor-1 in invasion and proliferation of HLE hepatocellular carcinoma cells, JPN J CANC, 90(7), 1999, pp. 747-752
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.