Urokinase-type plasminogen activator receptor (uPAR) expression is associated with T-stage and survival in urothelial carcinoma of the bladder

The urokinase-type plasminogen activator receptor (uPAR) mediates various cellular activities and is involved in proteolysis, angiogenesis, and inflammation. The objective of this study was to investigate the association between soluble uPAR (suPAR) levels and community-acquired pneumonia (CAP) severity. A commercial enzyme-linked immunosorbent assay (ELISA) was performed to measure the plasma suPAR levels in 67 healthy controls and 75 patients with CAP. Our results revealed that plasma suPAR levels were significantly elevated in patients with CAP compared with the controls, and antibiotic treatment was effective in reducing suPAR levels. The plasma suPAR levels were correlated with the severity of CAP based on the pneumonia severity index (PSI) scores. Furthermore, lipopolysaccharide (LPS)-stimulation significantly increased uPAR expression in RAW 264.7 macrophages. In conclusion, plasma suPAR levels may play a role in the clinical assessment of CAP severity; these findings may provide information on new targets for treatment of CAP.

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Rac Mediates Cytoskeletal Rearrangements and Increased Cell Motility Induced by Urokinase-Type Plasminogen Activator Receptor Binding to Vitronectin

The Journal of Cell Biology ◽

10.1083/jcb.152.6.1145 ◽

2001 ◽

Vol 152 (6) ◽

pp. 1145-1158 ◽

Cited By ~ 130

Author(s):

Lars Kjøller ◽

Alan Hall

Keyword(s):

Cell Motility ◽

Plasminogen Activator ◽

Malignant Tumors ◽

Leading Edge ◽

Dominant Negative ◽

Actin Reorganization ◽

Type Plasminogen Activator ◽

Upar Expression ◽

Urokinase Type Plasminogen Activator ◽

Plasminogen Activator Receptor

The urokinase-type plasminogen activator receptor (uPAR) is involved in the regulation of cell motility in a variety of cell types. We show here that expression of human uPAR in growing murine fibroblasts leads to a dramatic reorganization of the actin cytoskeleton. uPAR expression induces multiple rapidly advancing protrusions that resemble the leading edge of migrating cells. The cytoskeletal changes are independent of uPA and activation of the RGD-binding activity of integrins but require uPAR binding to vitronectin (VN). The actin reorganization is blocked by coexpression of dominant negative versions of either Rac (N17Rac) or p130Cas, but not by inhibitors of Cdc42 or Rho, and is accompanied by a Rac-dependent increase in cell motility. In addition, a fourfold increase in the level of activated Rac is induced by uPAR expression. We conclude that uPAR interacts with VN both to initiate a p130Cas/Rac-dependent signaling pathway leading to actin reorganization and increased cell motility and to act as an adhesion receptor required for these responses. This mechanism may play a role in uPAR-mediated regulation of cell motility at sites where VN and uPAR are co-expressed, such as malignant tumors.

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Clinical Significance of Urokinase-Type Plasminogen Activator Receptor (uPAR) Expression in Cancer

ChemInform ◽

10.1002/chin.200414278 ◽

2004 ◽

Vol 35 (14) ◽

Author(s):

Charles Edo de Bock ◽

Yao Wang

Keyword(s):

Plasminogen Activator ◽

Clinical Significance ◽

Type Plasminogen Activator ◽

Upar Expression ◽

Urokinase Type Plasminogen Activator ◽

Plasminogen Activator Receptor

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Circulating Forms of Urokinase-Type Plasminogen Activator Receptor in Plasma Can Predict Recurrence and Survival in Patients with Urothelial Carcinoma of the Bladder

Cancers ◽

10.3390/cancers13102377 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2377

Author(s):

Line H. Dohn ◽

Peter Thind ◽

Lisbeth Salling ◽

Henriette Lindberg ◽

Sofie Oersted ◽

...

Keyword(s):

Overall Survival ◽

Urothelial Carcinoma ◽

Tumour Tissue ◽

Recurrence Free Survival ◽

Cancer Specific Survival ◽

Free Survival ◽

Type Plasminogen Activator ◽

Urokinase Type Plasminogen Activator ◽

Plasminogen Activator Receptor ◽

Carcinoma Of The Bladder

Urothelial carcinoma of the bladder is a highly aggressive disease characterised by a very heterogeneous clinical outcome. Despite cystectomy, patients still have a high recurrence risk and shortened survival. Urokinase-type plasminogen activator receptor (uPAR) is present in tumour tissue specimens from patients with urothelial carcinoma. The different uPAR forms in blood are strong prognostic markers in other cancer types. We investigate the presence of different uPAR forms in tumour tissue and test the hypothesis that preoperative plasma levels of the uPAR forms predict recurrence free survival, cancer specific survival, and overall survival in patients treated with cystectomy for urothelial carcinoma. Using Western blotting we analyse neoplasia and adjacent benign-appearing urothelium from randomly selected patients for the presence of intact and cleaved uPAR forms. Prospectively collected preoperative plasma samples from 107 patients who underwent radical cystectomy for urothelial carcinoma are analysed. The different uPAR forms are measured by time-resolved fluorescence immunoassays. uPAR in tumour tissue from patients with urothelial carcinoma is demonstrated in both an intact and cleaved form. The different uPAR forms in plasma are all significantly associated with both recurrence free survival, cancer specific survival, and overall survival, high concentrations predicting short survival. uPAR (I) has the strongest association with a HR of 2.56 for overall survival. In the multivariable survival analysis uPAR (I) is significantly associated with cancer specific survival and overall survival.

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