UP-REGULATION OF UROKINASE-TYPE PLASMINOGEN-ACTIVATOR IN SQUAMOUS-CELL CARCINOMA OF HUMAN LARYNX

The expression of urokinase-type plasminogen activator (uPA) was inves tigated in squamous cell carcinoma of the human larynx. For this purpo se, tissue extracts from 25 matched samples of normal mucosa and neopl astic larynx were compared for the levels of uPA activity as evaluated by a chromogenic PA assay and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) zymography. Also, uPA antigen was quant ified by enzyme-linked immunosorbent assay (ELISA) in 19 cases. The re sults demonstrate a significant increase in the levels of uPA activity and protein in tumour tissue extracts, more pronounced in rumours wit h lymph node metastases. Immunohistochemistry performed on 70 biopsies showed that uPA positivity is present both in neoplastic cells and in fibroblast-like cells and macrophages. However, depending on the hist ological grading and invasive capacity of the tumour, a pronounced int ra- and intertumoral heterogeneity in uPA staining was observed. In si tu hybridisation confirmed the presence of uPA mRNA in both tumour and stromal cells. The present study provides experimental evidence for a role of uPA in the invasive growth of human laryngeal carcinoma.