Plasma Urokinase Receptor Levels in Patients With Colorectal Cancer: Relationship to Prognosis

Stephens, Ross W.; Nielsen, Hans Jørgen; Christensen, Ib Jarle; Thorlacius‐Ussing, Ole; Sørensen, Steen; Danø, Keld; Brünner, Nils

doi:10.1093/jnci/91.10.869

Cited by 262 publications

(198 citation statements)

References 23 publications

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“…Increased serum levels of different uPAR forms have been associated with a poor prognosis in various cancers. 64,65 Reports concerning the ability of circulating uPAR to detect PCa are conflicting. McCabe et al 66 did not find any significant association between uPAR levels and the presence of PCa whereas Steuber et al 67 recently showed that uPAR fragments were significant predictors of PCa on biopsy specimens of patients with an elevated PSA.…”

Section: Urokinase Plasminogen Activation Systemmentioning

confidence: 99%

New circulating biomarkers for prostate cancer

Bensalah

Lotan

Karam

et al. 2007

Prostate Cancer Prostatic Dis

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Section: Urokinase Plasminogen Activation Systemmentioning

confidence: 99%

New circulating biomarkers for prostate cancer

Bensalah

Lotan

Karam

et al. 2007

Prostate Cancer Prostatic Dis

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“…Under these conditions, uPAR is likely to be exposed to a proteolytic micro-environment in vivo where it may be solubilized by phospholipases or proteases, like plasmin, and even may enter the bloodstream, as has been implied by several authors (Ploug et al, 1992;Grøndahl-Hansen et al, 1995;Pappot et al, 1997;Stephens et al, 1997). Indeed, recent publications have shown that by measuring the soluble form of uPAR in peripheral blood important prognostic information in patients with colon (Stephens et al, 1999) or ovarian cancer (Sier et al, 1998) can be obtained. We are currently studying the prognostic role of soluble uPAR in blood samples obtained from patient undergoing surgery for primary breast cancer.…”

Section: Months Monthsmentioning

confidence: 99%

Prognostic impact of urokinase-type plasminogen activator receptor (uPAR) in cytosols and pellet extracts derived from primary breast tumours

et al. 2001

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Summary Using a previously developed enzyme-linked immunosorbent assay (ELISA), the levels of the receptor for urokinase-type plasminogen activator (uPAR) were determined in cytosols and corresponding membrane pellets derived from 878 primary breast tumours. The levels of uPAR in the pellet extracts were more than 3-fold higher than those measured in the cytosols (P < 0.001). Moreover, the uPAR levels in the two types of extracts were weakly, though significantly, correlated with each other (r S = 0.20, P < 0.001). In Cox univariate analysis, high cytosolic levels of uPAR were significantly associated with reduced overall survival (OS) and relapse-free survival (RFS). The levels of uPAR in pellet extracts appeared not to be related with patient survival. In multivariate analysis, elevated levels of uPAR measured in cytosols and pellet extracts were found to be independent predictors of poor OS, not RFS. The prediction of poor prognosis on the basis of high uPAR levels emphasizes its important role in plasmin-mediated degradation of extracellular matrix proteins during cancer invasion and metastasis.

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“…In human tumors, their high level is directly related to the decreased chances of disease-free survival (Reuning et al, 1998;Stephens et al, 1999;Dano et al, 2005). In some cancers, uPA and uPAR are expressed by cancer cells, whereas in others, they are expressed by stromal cells .…”

Section: Introductionmentioning

confidence: 99%

A direct link between expression of urokinase plasminogen activator receptor, growth rate and oncogenic transformation in mouse embryonic fibroblasts

et al. 2006

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In addition to its role in invasion and metastasis of several tumors, the multifunctional urokinase receptor uPAR (urokinase plasminogen activator receptor) is directly involved in the growth of several cancer cells in vitro and in vivo. We have compared growth rate and oncogenic transformation in wild-type (wt) or uPAR À/À mouse embryonic fibroblasts (MEFs). Surprisingly, uPAR À/À MEFs grew faster than wt MEFs. This agreed with elevated levels of cell cycle mediators like extracellular signal-regulated protein kinase, p38, AP1 and Cyclin D1. Infection with a uPAR retrovirus reverted the effect, decreasing the growth rate.When MEFs were transformed with H-Ras V12 and E1A oncogenes, the efficiency of transformation in uPAR À/À MEFs was higher than in wt. UPAR À/À MEFs grew faster at low serum, produced more colonies in agar and produced tumors in vivo in nude mice with a lower latency period. The properties of the heterozygous uPAR þ /À MEFs were always intermediate. We conclude therefore that in MEFs uPAR concentration controls cell proliferation and the transforming activity of some oncogenes.

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Plasma Urokinase Receptor Levels in Patients With Colorectal Cancer: Relationship to Prognosis

Cited by 262 publications

References 23 publications

New circulating biomarkers for prostate cancer

New circulating biomarkers for prostate cancer

Prognostic impact of urokinase-type plasminogen activator receptor (uPAR) in cytosols and pellet extracts derived from primary breast tumours

A direct link between expression of urokinase plasminogen activator receptor, growth rate and oncogenic transformation in mouse embryonic fibroblasts

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