MULTIFUNCTIONAL POTENTIAL OF THE PLASMINOGEN ACTIVATION SYSTEM IN TUMOR INVASION AND METASTASIS (REVIEW)

Tumor cell migration and invasion into the surrounding tissue depend-o n the invasive capacity of cells leading to the loosening of cell-cell and cell-substratum contacts via cell surface associated proteolytic enzyme systems. Plasmin is one of the enzymes involved in these comple x events. It is generated by the cleavage of the proenzyme plasminogen upon the action of the urokinase-type plasminogen activator (uPA). uP A is synthesized and secreted by tumor cells and normal cells and inte racts with a specific cell surface receptor (uPAR) thereby focalizing enzymatic activity to the cell surface. The activity of uPA is control led by plasminogen activator inhibitors type-1 and type-2. A strong st atistically independent prognostic impact has been attributed to uPA a nd its inhibitor PAI-1 in a variety of malignancies. Besides its prote olytic activity, uPA in concert with uPAR exert biological effects cha racteristic for molecules with signal transducing properties including chemotaxis, migration/invasion, adhesion, and mitogenesis.