Urokinase, also called urokinase-type plasminogen activator (uPA), is a serine protease involved in degradation of the extracellular matrix and possibly tumor cell migration and proliferation. uPA was originally isolated from human urine, but is present in several physiological locations, such as blood stream and the extracellular matrix. The most important inhibitors of uPA are PAI-1 and PAI-2, which inhibit the protease activity irreversibly. In the extracellular matrix, uPA is tethered to the cell membrane by its interaction to the urokinase receptor.
Elevated expression levels of uPA and several other components of the plasminogen activation system are found to be correlated with tumor malignancy. uPA is a potent marker of invasion and metastasis in a variety of human cancers associated with breast, stomach, colon, bladder, ovary, brain and endometrium. A specific polymorphism in uPA gene is implicated in late-onset Alzheimer disease and also with decreased affinity for fibrin-binding. uPA is used clinically as a thrombolytic agent in the treatment of severe or massive deep venous thrombosis, pulmonary embolism, myocardial infarction, and occluded intravenous or dialysis cannulas. It is also administered intrapleurally to improve the drainage of complicated pleural effusions and empyemas.