Variations of components of the plasminogen activation system with the cell cycle in benign prostate tissue and prostate cancer

Background: Components of the fibrinolytic system are involved in tumor cell invasion and metastasis. Previous investigations suggested a cell cycle‐dependent expression of urokinase‐type plasminogen activator (u‐PA) in epithelial cells. In order to determine a correlation of cell cycle phases with the fibrinolytic system, we investigated the expression of u‐PA, tissue‐type plasminogen activator (t‐PA), and plasminogen activator inhibitor type 1 (PAI‐1) in normal and tumor‐containing prostate extracts and analyzed a possible relationship with flow cytometry‐determined proliferative activity of the samples. Cell cycle phases were correlated with fibrinolytic parameters in prostate tissue. Methods: Samples were obtained from patients undergoing radical prostatectomy for prostate cancer and separated into two portions for DNA analysis and the detection of u‐PA, t‐PA, and PAI‐1. Flow cytometric analysis was performed according to the Vindelov technique. The concentrations of u‐PA, t‐PA, and PAI‐1 were determined from tissue extracts after homogenization by an enzyme‐linked immunosorbent assay (ELISA) technique. Results: Correlations of u‐PA and t‐PA expression with the frequency of G0/G1, S, G2M, S‐phase fraction (SPF), and proliferation index (PI) for normal prostate and prostate cancer revealed no significant correlation. The only significant finding was observed in normal tissue revealing a positive correlation between PAI‐1 expression and G0/G1 and a negative correlation with S‐phase, SPF, and PI. No dependence of PAI‐1 expression on different cell phases was found in prostate cancer. Furthermore, no significant correlation of u‐PA, t‐PA, and PAI‐1 with cell cycles in organ‐confined (