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

Abstract

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.

Role of Estrogen Receptor in the Regulation of Ecto-5′-Nucleotidase and Adenosine in Breast Cancer

“…3D). In contrast to the effects on eN, there was no effect of estradiol or antiestrogens on the expression of other glycosylphosphatidyl inositol-linked membrane proteins, urokinase-type plasminogen activator receptor or CD24 (two proposed markers for breast carcinoma) or Thy-1 (22)(23)(24). The lack of effect of estradiol on urokinase-type plasminogen activator receptor expression has also been reported in MDA-MB-231 cells stably expressing ER␣ (25).…”

uPAR and HER-2 gene status in individual breast cancer cells from blood and tissues

“…Overexpression of uPAR is associated with increased metastases, heightened malignancy and a shorter survival time (7)(8)(9)(10)(11)(12)(13)(14)(15). Indeed, overexpression of uPA, a ligand for uPAR, is the only breast cancer marker with Level of Evidence-1 for a poor prognosis (26)(27)(28).…”

“…However, it is well documented that uPA receptor (uPAR) overexpression is also associated with increased tumor aggressiveness and worse disease-free survival and overall survival in breast and other cancers (7)(8)(9)(10)(11)(12)(13)(14)(15). Very little is known about the regulation of uPAR expression.…”

“…In addition, other signaling pathways are activated to induce cellular proliferation, motility, and additional remodeling of the ECM. As a result, overexpression in breast cancer and many other cancers (7)(8)(9)(10)(11)(12)(13)(14)(15) is associated with a poor prognosis, and therapies targeting the uPA system are under development.…”

Real‐time quantitative PCR determination of urokinase‐type plasminogen activator receptor (uPAR) expression of isolated micrometastatic cells from bone marrow of breast cancer patients

“…Only the fraction of uPAR positive in tumor cells was positively correlated with tumor cells in bone marrow. uPAR expression has also been described as a pejorative prognostic factor in endometrial cancer, 16 -19 breast cancer [17][18][19] and gastric cancer, 20 -22 although contradictory results have been reported for ovarian cancer. 23 uPAR may be a marker to define a critical subpopulation of DTC.…”