Urokinase plasminogen activator in ovarian cancer

Invasion and metastasis require the destruction of the extracellular matrix and basement membranes to facilitate growth or migration of tumor cells into vascular and lymphatic spaces. These processes are mediated by proteolytic enzymes. Malignant cells produce urokinase which is a protease known to enhance the invasiveness of many tumor cells. The relationship between urokinase and various prognostic factors was investigated in 16 patients with epithelial ovarian cancer. Tissue concentrations of urokinase were measured in tumor cytosols using enzyme-linked immunoassays. Urokinase levels were lower in ovarian tumors of low malignant potential (median 9.5, range 3.5-18.3 pg/mg protein, n = 4) than invasive cancers (median 44.6, range 16.1-210.6 pg/mg protein, n = 12), p < 0.01. In the invasive carcinomas urokinase levels did not vary significantly with tumor stage or cell type. Grade 3 tumors had higher levels of urokinase (median 120.4, range 21.4-397.1 pg/mg protein, n = 6) than grade 1 and 2 tumors (median 29.2, range 16.1-51.8 pg/mg protein, n = 6), p < 0.05. Urokinase levels were higher in recurrent (median 120.4, range 51.8-210.6 pg/mg protein, n = 4) than in primary (median 29.2, range 16.1-97.1 pg/mg protein, n = 8) tumors, p < 0.05. These results support the hypothesis that urokinase plays a role in invasion and metastasis of ovarian epithelial cancers and suggest that tissue levels of urokinase may have prognostic value.