title: Rational targeting of the urokinase receptor (uPAR): development of antagonists and non-invasive imaging probes.
abstract: In the last two decades, the urokinase-type plasminogen activator receptor (uPAR) has been implicated in a number of human pathologies such as cancer, bacterial infections, and paroxysmal nocturnal hemoglobinuria. The primary function of this glycolipid-anchored receptor is to focalize uPA-mediated plasminogen activation at the cell surface, which is accomplished by its high-affinity interaction with the growth factor-like domain of uPA. Detailed insights into the molecular basis underlying the interactions between uPAR and its two bona fide ligands, uPA and vitronectin, have been obtained recently by X-ray crystallography and surface plasmon resonance studies. Importantly, these structural studies also define possible druggable target sites in uPAR for small molecules and provide guidelines for the development of reporter groups applicable for non-invasive molecular imaging of uPAR expression in vivo by positron emission tomography. In this review, we will discuss recent advances in our perception of the structure-function relationships of uPAR ligation and how these may assist translational research in preclinical intervention studies of uPAR function.
authors.affiliation: Finsen Laboratory, Copenhagen Biocenter, Rigshospitalet, Copenhagen, Denmark.
authors.forename: M C
authors.initials: MC
authors.lastname: Kriegbaum
authors.forename: M
authors.initials: M
authors.lastname: Persson
authors.forename: L
authors.initials: L
authors.lastname: Haldager
authors.forename: W
authors.initials: W
authors.lastname: Alpízar-Alpízar
authors.forename: B
authors.initials: B
authors.lastname: Jacobsen
authors.forename: H
authors.initials: H
authors.lastname: Gårdsvoll
authors.forename: A
authors.initials: A
authors.lastname: Kjær
authors.forename: M
authors.initials: M
authors.lastname: Ploug
mesh_terms: D000818:Animals; D020868:Gene Silencing; D006801:Humans; D015335:Molecular Probes; D058990:Molecular Targeted Therapy; D064847:Multimodal Imaging / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods; D011487:Protein Conformation; D055293:Receptors, Urokinase Plasminogen Activator / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013045:Species Specificity; D014057:Tomography, X-Ray Computed; D057170:Translational Research, Biomedical; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D019096:Vitronectin / Q000737:chemistry / Q000378:metabolism
chemical_list: D015335:Molecular Probes; D055293:Receptors, Urokinase Plasminogen Activator; D019096:Vitronectin; D014568:Urokinase-Type Plasminogen Activator