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

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of 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 that degraded the extracellular matrix in process of invasion and metastasis. In order to study the kinetics of uPA cellular expression during this process, we used specific polyclonal antibodies against uPA in an immunohistochemistry assay in liver sections from a HCC in rats. The neoplastic transformation induced with this model was preceded by the appearance of numerous hyperplastic nodules during early stages, after time lesions progressed to well-differentiated HCC. The morphological changes of premalignant and malignant 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 transpeptidase showed correlationship with the histological findings. Our results suggest that the increase in the uPA expression should not only be considered as the hallmark of metastasis, but may also be related to early events in the neoplastic transformation and with the proliferation of vessels and biliary ducts.