Urokinase plasminogen activator and urokinase plasminogen activator receptor in breast cancer

Duggan, Catherine; Maguire, Teresa; McDermott, Enda; O’Higgins, N.; Fennelly, J. J.; Duffy, Michael J.

doi:10.1002/ijc.2910610502

Cited by 136 publications

(98 citation statements)

References 17 publications

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“…Our findings with regard to uPA and uPAR overexpression are in agreement with previous studies carried out in other solid tumours which indicate that both factors are also often concomitantly present at the protein level and that the presence of uPA and uPAR may contribute to tumour invasion and tumour spread and thereby to worse prognosis (Del Vecchio et al, 1993;Duggan et al, 1995).…”

Section: Discussionsupporting

confidence: 93%

“…However, only a few studies of colon (Pyke et al, 1991) and ovarian carcinomas (Schmalfeldt et al, 1995) and of breast (Del Vecchio et al, 1993;Duggan et al, 1995) adenocarcinomas have investigated the simultaneous expression of uPA and its receptor, showing that both factors appear to play a role in the process of tumour invasion and metastasis (Dano et al, 1992). Because of the high metastatic and invasive potential of human pancreatic cancer cells, we have analysed in the present study the concomitant expression of uPA and its receptor in human pancreatic adenocarcinomas.…”

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confidence: 99%

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Enhanced expression of urokinase plasminogen activator and its receptor in pancreatic carcinoma

Cantero

Frieß²,

Deflorin³

et al. 1997

Br J Cancer

186

126

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Summary Urokinase plasminogen activator (uPA) is a serine proteinase that has been suggested to play an important role in cancer invasion and metastasis. It binds to a specific membrane receptor denominated uPA receptor (uPAR Pancreatic cancer has one of the poorest prognoses of all gastrointestinal malignancies, being the fourth or fifth leading cause of cancer-related deaths in Western industrialized countries (Bomman et al, 1994). Gudjonsson (1987), in his classical review of 37 000 patients with pancreatic cancer, demonstrated an overall survival rate of 0.4% and a median survival time of 5 months after the diagnosis was established. Once pancreatic cancer is clinically evident, it progresses at a rapid rate, and metastasis has usually occurred at the time of diagnosis. Consequently, many patients are not resectable at presentation, and the overall resection rate is often less than 30% (Gudjonsson 1987;Bomman et al, 1994). The mechanisms that regulate this aggressive growth behaviour in pancreatic cancer are not at all clear. Recently, it has been shown in pancreatic cancer that the concomitant overexpression of the epidermal growth factor (EGF) receptor and its ligands EGF-, TGF-alpha (Korc et al, 1992;Yamanaka et al, 1993a) and/or amphiregulin (Ebert et al, 1994a; Yokoyama et al., 1995a) is associated with shorter post-operative survival following tumour resection. In addition, enhanced expression of c-erbB-3 (Friess et al, 1995), TGF-fs and basic fibroblast growth

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Section: Discussionsupporting

confidence: 93%

mentioning

confidence: 99%

Enhanced expression of urokinase plasminogen activator and its receptor in pancreatic carcinoma

Cantero

Frieß²,

Deflorin³

et al. 1997

Br J Cancer

186

126

View full text Add to dashboard Cite

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“…In this study, the prognostic value of uPAR in primary breast carcinomas as documented in earlier investigations by Duggan et al (1995). Grøndahl-Hansen et al (1995), Bouchet et al (1999) and Foekens et al (2000) could be confirmed, high levels of uPAR being associated with poor disease outcome.…”

Section: Months Monthssupporting

confidence: 83%

“…Relatively few studies have reported on the clinical relevance of uPAR in human cancer, though elevated levels of uPAR have been shown to predict poor disease outcome in breast cancer as well (Duggan et al, 1995;Bouchet et al, 1999;Foekens et al, 2000). Recently, we evaluated the clinical relevance of uPA, tPA and PAI-1 determined by a newly developed ELISA in cytosolic extracts as well as in corresponding detergent extracts of pellets obtained after ultracentrifugation when preparing the cytosolic fractions (De Witte et al, 1999a, b).…”

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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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“…enzyme-linked immunosorbent assay uPA, uPA receptor (uPAR), tPA, PAI-I and PAI-2 were all assayed as described previously (Duggan et al, 1995). Briefly, tumours were homogenized in 50 mM Tris buffer (pH 7.4) containing 1 mM monothiolglycerol.…”

mentioning

confidence: 99%

Plasminogen activator inhibitor type 2 in breast cancer

Duggan

Kennedy²,

Kramer³

et al. 1997

Br J Cancer

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Summary The serine protease urokinase plasminogen activator (uPA) is causally involved in cancer invasion and metastasis. Activity of this protease in vivo is controlled principally by two inhibitors, one of which is plasminogen activator inhibitor type 2 (PAI-2). In this study, we show that PAI-2 levels were significantly higher in primary breast carcinomas (n = 152) than benign breast tumours (n = 18). In the primary cancers, PAI-2 levels correlated weakly but significantly with those of uPA and PAI-1, but not with tissue type plasminogen activator (tPA) or uPA receptor (uPAR) levels. Using Northern blotting, mRNA for PAI-2 was&found in 28.6% of 49 primary breast cancers. In contrast to findings at the protein level, PAI-2 mRNA levels failed to correlate with those for uPA or PAI-1. After immunocytochemistry with primary cancers, PAI-2 was detected predominantly in the malignant cells of primary carcinomas but was also present in stromal cells. Using the median value as a cut-off point, PAI-2 showed no significant relationship with either disease-free interval or overall survival. However, using an optimum cut-off value, patients with low levels of PAI-2 had a worse outcome than those with a high level. We conclude that, unlike PAI-1, high levels of PAI-2 may be a favourable prognostic marker in breast cancer.

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Urokinase plasminogen activator and urokinase plasminogen activator receptor in breast cancer

Cited by 136 publications

References 17 publications

Enhanced expression of urokinase plasminogen activator and its receptor in pancreatic carcinoma

Enhanced expression of urokinase plasminogen activator and its receptor in pancreatic carcinoma

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

Plasminogen activator inhibitor type 2 in breast cancer

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