A. Nieto-rodriguez et al., Expression of urokinase-type plasminogen activator in an experimental model of hepatocarcinoma, TOXICOLOGY, 161(1-2), 2001, pp. 13-23
Hepatocellular carcinoma (HCC) is the most common primary malignant tumor o
f the liver. Molecular genetic analyses have clarified that accumulation of
genome changes provides important steps in carcinogenesis. Urokinase type
plasminogen activator (uPA) forms part of an important enzymatic system tha
t degraded the extracellular matrix in process of invasion and metastasis.
In order to study the kinetics of uPA cellular expression during this proce
ss. we used specific polyclonal antibodies against uPA in an immunohistoche
mistry assay in liver sections from a HCC in rats. The neoplastic transform
ation induced with this model was preceded by the appearance of numerous hy
perplastic nodules during early stages, after time lesions progressed to we
ll-differentiated HCC.: The morphological changes of premalignant and malig
nant lesions were associated with a progressive increment of uPA expression
, which reached its peak at 5 and 6 months after the administration of the
carcinogenic drugs. Of the enzymatic markers analyzed, the gamma glutamyl t
ranspeptidase showed correlationship with the histological findings. Our re
sults suggest that the increase in the uPA expression should not only be co
nsidered as the hallmark of metastasis, but may also be related to early ev
ents in the neoplastic transformation and with the proliferation of vessels
and biliary ducts, (C) 2001 Elsevier Science II eland Ltd. All rights rese
rved.