The Urokinase Plasminogen Activator System in Human Cancers: An Overview of Its Prognostic and Predictive Role

Urokinase plasminogen activator (uPA) system regulates extracellular matrix remodelling by activating ubiquitous protease plasmin in many important physiological processes. The system components include uPA, plasminogen activator inhibitors (PAIs) and uPA receptor (uPAR). Besides its role in physiological processes, uPA system is active in most tumour types where its aberrant regulation has been associated with the development of metastatic phenotype. In vitro and in vivo studies have shown that the over-expression of uPA, PAI-1 and uPAR not only enhances tumour cell invasion capacity and metastasis, but also corresponds to a higher risk of disease correlating with traditional clinicopathological features which makes them potential prognostic biomarkers and therapeutic targets in a wide range of human malignancies. This review focuses on uPA system's prognostic and predictive role in several types of human cancers, summarizing its activities in cancer development and highlighting the importance of addressing all unanswered questions before bridging the gap between laboratory findings to clinic use of uPA system's components as cancer biomarkers.