Urokinase-type plasminogen activator in carcinomatous pleural fluid

Urokinase-type plasminogen activator (u-PA) is known to be secreted by malignant cells during proliferation and migration, and is associated with tumour cell invasion and metastasis. This study was undertaken to evaluate whether u-PA is significantly increased in carcinomatous pleural fluids compared to those due to other aetiologies, and to identify the cells in the pleural space that are involved in its accumulation. Using an enzyme-linked immunosorbent assay, we quantified u-PA in the pleural fluid specimens of 40 patients with carcinomatous pleuritis, 18 with tuberculosis, 18 with parapneumonic pleuritis and 11 with congestive heart failure (CHF). The level of u-PA was elevated in carcinomatous pleural fluid compared with the level in transudative pleural fluid from patients with CHF (p<0.0001). The levels of u-PA were not statistically different between patients with cancer and tuberculosis, or between patients with cancer and pneumonia. The levels of u-PA in patients who did not respond to chemical pleurodesis were significantly higher than those who had complete response (p=0.0001). In immunocytochemical and immunoblotting studies, cancer cells in pleural fluids as well as mesothelial cells contained u-PA. u-PA was detected in the culture supernatants of viable pleural cells in the majority of patients with carcinomatous pleuritis. Our results suggest that local release of urokinase-type plasminogen activator by viable cells, including cancer cells and mesothelial cells, may affect the levels of urokinase-type plasminogen activator in pleural fluids.