Urokinase-type plasminogen activator and its receptor: new targets for anti-metastatic therapy?

Urokinase-type plasminogen activator (uPA) and its receptor are instrumental in cell invasion and metastasis; their high levels of expression in human tumours correlates with a high risk of recurrence. uPA has a pleiotropic effect on cell migration and spreading in vivo and in vitro through the activation of plasminogen or other protein factors at the cell surface or in the extracellular matrix. Three specific inhibitors, with different tissue-specificities and regulatory properties, modulate cell-surface exposure of uPA activity. Overall, uPA is at the centre of a complex system affecting cell movement and invasiveness, and inhibition of uPA is now a goal of anti-metastatic therapy. The role of uPA and its inhibition are discussed in this review by Francesca Fazioli and Francesco Blasi.