Urokinase receptor variants in tissue and body fluids.
The cellular receptor for urokinase, urokinase-type plasminogen activator receptor (uPAR) plays a central role in localizing its ligand, urokinase-type plasminogen activator (uPA) and thereby the plasminogen activation to the cell surface. uPA converts the proenzyme plasminogen to plasmin, which is involved in degradation of the extracellular matrix. In addition, uPA also cleaves uPAR, liberating the ligand-binding domain I, uPAR(I) and leaving the cleaved form, uPAR(II-III) on the cell surface. This cleavage inactivates the binding potential of uPAR toward uPA and vitronectin. uPAR can be shed from the cell surface and both intact and cleaved uPAR variants have been identified in tissue and body fluids. Identification and characterization of cleaved uPAR variants are dependent on monoclonal antibodies with known epitope specificity. Some of these have also been useful for the immunohistochemical localization of uPAR in tumor tissue. A number of immunoassays have been designed to measure uPAR and the collective amounts of all uPAR forms measured by enzyme-linked immunosorbent assay (ELISA) in tumor lysates or blood correlate to prognosis in several forms of cancer. However, the amounts of uPAR(I) and uPAR(II-III) may be directly related to the uPA activity and therefore be even stronger prognostic markers. Immunoassays measuring the individual uPAR forms have recently been designed and can be used to investigate this. This chapter is focused on the mechanism of uPAR cleavage and characterization and identification of the different uPAR forms in biological tissues and body fluids using immunologic methods. Monoclonal antibodies against uPAR are reviewed as well as different immunoassays used to investigate the prognostic potential of uPAR. Finally, an overview of the localization and prognostic significance of uPAR in different cancers and other malignancies is included.
Finsen Laboratory, Strandboulevarden 49, DK-2100 Copenhagen Ø, Denmark.
Gunilla
G
Høyer-Hansen
Ida Katrine
IK
Lund
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001826:Body Fluids / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007118:Immunoassay; D009369:Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator