UPAR

In vitro invasion through trans-well polycarbonate membranes 8.0 pm pores UPAR expression UPA expression PA-1 expression... 

D10. Dumler, I. T., Petri, T., and Schleuning, W. D., Interaction of urokinase-type plasminogen activator (uPA) with its cellular receptor (uPAR) induces phosphorylation on tyrosine of a 38 kDa protein. FEBS Lett. 322, 37-40 (1993). 

Berg D, Wolff C, Malinowsky K et al (2012) Profiling signalling pathways in formalin-fixed and paraffin-embedded breast cancer tissues reveals cross-talk between EGFR, HER2, HERS and uPAR. J CeU Physiol 227 204-212... 

Full-Length, Glycolipid-Anchored uPAR, uPAR(I-III). 68... 

In addition to binding to uPAR(I-III), uPA can cleave uPAR(I-III) in the linker region between domains I and II, liberating domain I and leaving the cleaved form, uPAR(II-III) on the cell surface [16, 17]. uPAR(I-III) is shed from the cell surface by cleavage at or near the glycolipid anchor, and the soluble form, suPAR(I-III) as well as the cleaved soluble form, suPAR(II-III) have been identified in biological fluids [8, 18-22], Two crystal structures of a soluble form of the human uPAR(I-III) have been reported [23, 24]. 

This chapter will concentrate on the different uPAR forms, how they are generated, in what tissues and body fluids they have been detected, and how they may be measured in patient samples by immunoassays. The mAbs used for assay design and immunohistochemistry will be characterized with respect to domain specificity. Finally, an overview of the prognostic findings that has been made in relation to several types of cancers is given. 

Twenty years ago, a high-affinity-binding site for uPA was demonstrated on the surface of peripheral blood monocytes and cultured cells of the human histiocytic lymphoma cell line, U937 [46]. The expression of uPAR on the cell surface of many cell types has since then been demonstrated, including a variety of neoplastic cell lines as well as nonneoplastic cells such as neutrophils, macrophages, keratinocytes, placental trophoblasts, endothelial, and smooth muscle cells [7, 33, 47-51]. The human uPAR gene has been mapped to chromosome 19ql.3 [52]. 

The uPAR protein was initially purified from lysates of phorbol ester-stimulated U937 cells by affinity chromatography using diisopropyl fluoro-phosphates (DFP)-inactivated uPA [53, 54]. uPAR is anchored in the plasma membrane by a glycosylphosphatidylinositol (GPI) moiety and it consists of 283 amino acids in its processed form [55, 56]. The protein is composed of three domains and each domain contains 90 amino acids. The domains are connected by linker regions with a length of 15-20 amino acids [57, 58]. The disulfide bonds in the N-terminal domain I have been experimentally determined and the pattern of cysteine residues in the sequence has revealed... 

In the elegant studies by Zhou and coworkers, simultaneous overexpression of catalytically active uPA and uPAR in keratinocytes in the presence of plasminogen resulted in a pathological phenotype of the skin characterized by extensive alopecia, induced by involution of the hair follicles, epidermal thickening, and subepidermal blisters [4,68]. No skin phenotype was evident in mice with targeted overexpression of either uPA or uPAR alone, of catalytically inactive uPA together with uPAR, or in the absence of plasminogen. 

In addition to its role in pericellular proteolysis, uPAR(I-III) plays a role in cell adhesion by binding to the extracellular matrix protein vitronectin [69]. There has been some controversy as to where the binding site for vitronectin is located in the uPAR structure. However, the domain I-specific mAbs, R3 and R5, prevented binding of vitronectin to cell surface-expressed uPAR(I-III) as well as to soluble uPAR(I-III), whereas the mAbs, R2 and... 

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