Methods to Analyze the Effects of the Urokinase System on Cancer Cell Adhesion, Proliferation, Migration, and Signal Transduction Events

For cellular-invasive processes during a variety of physio- and pathophysiological events, including cancer, a fine-tuned balance between the formation and loosening of cell adhesive contacts has to occur, implicating the action of pericellular proteases; among those, the serine protease, urokinase-type plasminogen activator (uPA), its inhibitor PAI-1, and its cellular receptor uPA-R (CD87). Apart from its proteolytic functions, the uPA system is endowed with properties affecting the proliferative, adhesive, and migratory cellular phenotype. These events depend on signal transduction pathways known to be activated downstream of uPA/uPA-R cell surface interaction and require physical and functional cooperation and crosstalk with cell adhesion and signaling receptors of the integrin superfamily.