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.
Binder
B R
BR
Department of Clinical Experimental Physiology, University of Vienna, Austria.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D010958:Plasminogen / Q000378:metabolism*; D015849:Plasminogen Inactivators / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*
D004792:Enzyme Precursors; C524898:PLAUR protein, human; D015849:Plasminogen Inactivators; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010958:Plasminogen; D014568:Urokinase-Type Plasminogen Activator