Urokinase-type Plasminogen Activator System and Breast Cancer (Review)

Malignant tumors have a capacity to degrade the extracellular matrix (ECM) by controlled proteolysis. One proteolytic system involved in these processes is the urokinase-type plasminogen activator (uPA) system, which consists of uPA, uPA receptor (uPAR) and uPA inhibitors 1 and 2 (PAI-1 and PAI-2). In the past two decades, study of the uPA system in human breast cancer has yielded valuable insights. Increased levels of uPA, PAI-1 and uPAR have been reported to be associated with poor prognosis in patients with breast cancer. Furthermore, uPA and PAI-1 may be new prognostic markers for axillary node-negative patients. To date, a growing body of evidence has suggested that uPA system promotes tumor metastasis by several different mechanisms, not just by breaking down the ECM. This article is focused on reviewing the current understanding of uPA system members as prognostic markers in breast cancer, and their cellular localization and tissue distribution. Correlations of the uPA system with other informative markers of breast cancer are also discussed.