The concentration of the cleaved suPAR forms in pre- and postoperative plasma samples improves the prediction of survival in colorectal cancer: A nationwide multicenter validation and discovery study.

Background And Objectives: The aim was to evaluate the prognostic biomarker potential of the soluble urokinase-type plasminogen activator receptor (suPAR) in plasma samples collected pre- and postoperatively from patients resected for colorectal cancer (CRC).

Methods: Patients with CRC were recruited prospectively at six centers from 2006 to 2008. Preoperative plasma samples were available from 494 patients and from 328 of these patients at 6 months postoperatively.

Identifying a potential biomarker for primary focal segmental glomerulosclerosis and its association with recurrence after transplantation.

Background: We investigated circulating levels of individual soluble urokinase plasminogen activation receptor (suPAR) forms to determine if specific circulating fragments of suPAR (II-III) and (I) can better serve as clinical biomarkers for focal segmental glomerulosclerosis (FSGS) and the risk of recurrence after transplantation.

Materials And Methods: Serum levels of intact suPAR and its cleaved forms were measured with two assays, ELISA and TR-FIA.

Results: suPAR levels in healthy controls were significantly lower than those who had glomerular diseases but were not significantly different between FSGS patients and glomerular controls.

The soluble urokinase plasminogen activator receptor and its fragments in venous ulcers.

Objective: Activation of proteolytic mechanisms at the cell surface through the activity of urokinase-type plasminogen activator (uPA) bound to its receptor, uPAR, is an important process in wound healing. The soluble forms of uPAR (suPAR and its fragments I, II, and III) have nonproteolytic functions that include chemotaxis, adhesion, and proliferation, which also have a role in wound healing. The aim of this study was to determine whether suPAR and its cleaved fragments are present in venous ulcers and whether their levels are associated with healing.

First-in-human uPAR PET: Imaging of Cancer Aggressiveness.

A first-in-human clinical trial with Positron Emission Tomography (PET) imaging of the urokinase-type plasminogen activator receptor (uPAR) in patients with breast, prostate and bladder cancer, is described. uPAR is expressed in many types of human cancers and the expression is predictive of invasion, metastasis and indicates poor prognosis. uPAR PET imaging therefore holds promise to be a new and innovative method for improved cancer diagnosis, staging and individual risk stratification.

Urokinase receptor cleavage correlates with tumor volume in a transgenic mouse model of breast cancer.

The urokinase plasminogen activator system plays a key role in tissue degradation during cancer invasion. The linker region between domains I and II of the intact, three domain urokinase receptor uPAR(I-III) is highly susceptible to proteolytic cleavage and the resulting cleaved uPAR forms are strong prognostic biomarkers in several types of cancer, i.e.

Circulating intact and cleaved forms of the urokinase-type plasminogen activator receptor: biological variation, reference intervals and clinical useful cut-points.

Background: High levels of circulating forms of the urokinase-type plasminogen activator receptor (uPAR) are significantly associated to poor prognosis in cancer patients. Our aim was to determine biological variations and reference intervals of the uPAR forms in blood, and in addition, to test the clinical relevance of using these as cut-points in colorectal cancer (CRC) prognosis.

Methods: uPAR forms were measured in citrated and EDTA plasma samples using time-resolved fluorescence immunoassays.

Urokinase-type plasminogen activator receptor (uPAR) on tumor-associated macrophages is a marker of poor prognosis in colorectal cancer.

Patients were identified from a population-based prospective study of 4990 individuals with symptoms associated with colorectal cancer (CRC). A total of 244 CRC tissue samples were available for immunohistochemical staining of uPAR, semiquantitatively scored at the invasive front, and in the tumor core on cancer cells, macrophages, and myofibroblasts. In addition, the levels of the intact and cleaved uPAR-forms in blood from the same patients are evaluated in this study.

uPAR as anti-cancer target: evaluation of biomarker potential, histological localization, and antibody-based therapy.

Degradation of proteins in the extracellular matrix is crucial for the multistep process of cancer invasion and metastasis. Compelling evidence has demonstrated the urokinase receptor (uPAR) and its cognate ligand, the urokinase plasminogen activator (uPA), to play critical roles in the concerted action of several proteolytic systems in generation of a high proteolytic potential required for tissue remodeling processes. uPAR is additionally cleaved by uPA on the cell surface, liberating domain I, resulting in abrogated pericellular proteolysis.

A new assay for measurement of the liberated domain I of the urokinase receptor in plasma improves the prediction of survival in colorectal cancer.

Background: The liberated domain I of the urokinase plasminogen activator receptor [uPAR(I)] is a significant prognostic marker in lung and ovarian cancer, although the uPAR(I) concentration is below the limit of quantification (LOQ) in a substantial proportion of patient samples (Lung Cancer 2005;48:349-55; Clin Cancer Res 2008;14:5785-93; APMIS 2009;117:755-61). This study was undertaken to design an immunoassay with improved functional sensitivity for measuring uPAR(I) and to evaluate the prognostic value of uPAR(I) for colorectal cancer (CRC) patients.

Methods: Surface plasmon resonance analysis identified 2 monoclonal antibodies, R3 and R20, that simultaneously bind to the liberated uPAR(I) but not to intact uPAR.

Soluble urokinase-type plasminogen activator receptor forms in plasma as markers of atherosclerotic plaque vulnerability.

Objectives: : To test if circulating forms of the soluble urokinase-type plasminogen activator receptor (suPAR) are potential biomarkers of plaque vulnerability.

Design And Methods: : Plasma concentrations of suPAR(I-III), suPAR(II-III) and uPAR(I) were measured by time-resolved fluorescence immunoassays in Caucasian patients operated for symptomatic carotid atherosclerosis (n=255). Local suPAR release from plaques into the circulation was assessed in plasma passing retrogradely over the plaque in the carotid artery, collected during surgery (n=7).