Expression of urokinase-type plasminogen activator in an experimental model of hepatocarcinoma

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.