It has now been well documented that urokinase-type plasminogen activator (uPA) and its receptor (uPAR) play a central role of fibrinolysis at cell surfaces. Further, the importance of this finding resides in various cellular regulation of fibrinolysis mediated by cell surface bound inhibitors and other fibrinolytic proteases. Other than those, members of a family of matrix metalloproteinases (MMP) either tightly or loosely bound to cell membranes are also intriguing in the efficient destraction of a surrounding extracellular matrix (ECM) when invasive tumor cells are spreading or tissues are remodeling.
Plasminogen activators activate plasminogen as well as some members of latent MMPs. Thus, plasminogen activators and MMPs are thought to be functionally crossoverd at cell surfaces. Those local membrane structures such as adhesion plaque and invadopodia as well may be important biological architectures, where both the receptor, binding sites for plasminogen and other proteolytic enzymes are localized. The former is functioning not only for cell adhesion, but for cellular locomotion, being able to degrade ECM via the activation of membrane bound plasminogen. The latter appears to be organized when invasive tumor cell moves across pores of an ECM-coated invasion chamber by breaching out the proteins. Therefore, both are thought to be active parts of the cellular membrane (domains) being able to interact locally with an ECM area composed of a suprastructure of networks of various monomer types of glycoproteins, such as collagen type IV, proteoglycans and laminin.
Here, I briefly describe the background of uPA/uPAR system at the level of cell and molecular biology and further hypothesize that interactions of the two structural domains are also essentially functional motifs; a driving force of the local hydorlysis of ECM and importance of uPA/uPAR dependent locomotion for invasive spread of tumor cell across basement membrane.
