Current Pharmaceutical Design - Volume 9, Issue 19, 2003

Urokinase type plasminogen activator (uPA) activates plasminogen to plasmin and is often associated with diseases where tissue remodeling is essential (e.g. cancer, macular degeneration, atherosclerosis). We discuss some of the mechanisms of uPA action in diseases, and evidence that some of the early uPA inhibitors can modulate the progression of these diseases. Recently, a number of research groups have discovere Read More

Degradation of the extracellular matrix plays an important role in a number of normal and pathological conditions involving active tissue remodeling such as postlactational mammary gland involution, wound healing and tumor invasion and metastasis. The expression of a high-affinity, glycolipid-anchored receptor for the urokinase-type plasminogen activator (uPAR) is often up-regulated during such tissue remodeling e Read More

In cancer, increased levels of the tumor-associated serine protease uPA (urokinase-type plasminogen activator) and its receptor uPAR (CD87) are linked to tumor progression, metastasis, and shortened survival in patients afflicted with this disease. Strong clinical and experimental evidence has accumulated that the cell surface interaction of uPA with uPAR facilitates extravasation and intravasation of cancer cells by regulating lo Read More

Plasminogen activator inhibitor-1 (PAI-1) is the principal inhibitor of urokinase type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA), and as such is thought to play an important role in the regulation of extracellular matrix remodeling. In blood, PAI-1 is bound to the adhesion protein vitronectin and is associated with vitronectin in fibrin clots and the provisional matrix. Elevated levels of PAI-1 are assoc Read More

Urokinase receptors (uPAR) were initially thought to function simply as a mechanism to concentrate the urokinase / plasmin system toward the cell surface. However, extensive evidence has accumulated that this glycolipidanchored receptor also functions in both the adhesive and signaling pathways of many migratory cells. Mechanisms by which uPAR exercises these functions involve complexing with other membrane prot Read More