Influence of urokinase on cell proliferation and invasion.

The urokinase-dependent plasminogen activating system is regulated not only by zymogen to enzyme conversion of pro-urokinase and inhibition of the active enzyme by plasminogen activator inhibitors, but also by regulated expression of urokinase receptors on the cell surface. Receptor-bound pro-urokinase in turn becomes activated and is capable of activating plasminogen probably bound site by site to urokinase to a cell surface receptor. Plasmin by itself or via activation of pro-collagenase to collagenase is capable of degrading the extracellular matrix, in turn mediating processes like invasion, metastasis and tumour growth. In addition, in some cell lines the urokinase-dependent system mediated via receptor-bound active urokinase is also capable of eliciting a mitogenic response of the cells. Therefore, the urokinase-dependent plasminogen activating system might not only be responsible for mediating extravascular proteolysis but might also be an autocrine mitogen for some cell lines.