Increased Cell-surface Urokinase in Advanced Ovarian Cancer

Abstract

Urokinase‐type plasminogen activator (uPA), uPA receptors, and cathepsin B were quantitatcd by using an immunological method, enzyme‐linked immunosorbent assay, and amidolytic activity assays in 15 malignant and 10 benign epithelial ovarian tumors. The levels of uPA and uPA receptors, as well as cathepsin B, were found to be higher in membrane preparations obtained from malignant tumors than in those obtained from benign tumors. Acid‐treated membranes acquired the ability to bind uPA, indicating that uPA is bound to a specific surface receptor that is not completely saturated. Levels of single‐chain uPA (pro‐uPA) and high‐molecular‐weight uPA in membrane preparations were measured by immunoadsorbent‐amidolytic assay. The finding of a significant increase in amidolytic activity following activation of uPAs by plasmin suggested that less than half (30–40%) of all membrane immunoreactive uPAs is present in the enzymatically inactive pro‐uPA form. In the membranes of malignant tumors, levels of uPA receptor and cathepsin B did not vary with stage of disease. On the other hand, we found that the level of receptor‐bound uPA antigen/activity was significantly increased in advanced malignant tumors. Receptor‐bound uPA may play an important role in determining invasive potential of tumor cells. Since ovarian cancer cells produce both pro‐uPA and cathepsin B, the possibility of activation of tumor cell‐derived pro‐uPA by cellular protease cathepsin B must be considered.