Intact and cleaved uPAR forms: diagnostic and prognostic value in cancer.
The cellular receptor for urokinase, uPAR, localizes its ligand, uPA, and thereby the plasminogen activation, to the cell surface. uPA also cleaves uPAR, liberating the ligand-binding domain I, and thereby inactivates the binding potential of uPAR for both uPA and vitronectin. The uPA-catalyzed cleavage of uPAR is fast on the cell surface, when uPA is bound to a neighboring uPAR molecule. uPAR can be shed from the cell surface. However, the soluble form cannot be cleaved by uPA. Glycolipid-anchored and soluble forms of intact, uPAR(I-III), and cleaved receptor, uPAR(II-III) and uPAR(I), have been identified in tissue and body fluids. It is well-established, that the total amount of all uPAR forms is a strong prognostic marker in different types of cancer. Using immunoassays, measuring the individual uPAR forms, has revealed that the cleaved uPAR forms are even stronger prognostic markers and have diagnostic utility. This review will focus on the mechanism of uPAR cleavage and the functional consequences, as well as the clinical applicability of cleaved uPAR forms.
Finsen Laboratory, Rigshospitalet section 3735, Copenhagen Biocenter, Ole Maaloes Vej 5, DK-2200 Copenhagen N, Denmark.
Morten G
MG
Rasch
Ida K
IK
Lund
Charlotte E
CE
Almasi
Gunilla
G
Hoyer-Hansen
D004789:Enzyme Activation; D005342:Fibrinolysis; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis* / Q000503:physiopathology; D010446:Peptide Fragments / Q000032:analysis; D010958:Plasminogen / Q000378:metabolism; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator
C524898:PLAUR protein, human; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010958:Plasminogen