Expression of plasminogen activator inhibitors type 1 and type 3 and urokinase plasminogen activator protein and mRNA in breast cancer

2007 ◽  
Vol 120 (5) ◽  
pp. 753-762 ◽  
Author(s):  
Remedios Castelló ◽  
Jose M. Landete ◽  
Francisco España ◽  
Carlos Vázquez ◽  
Carlos Fuster ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Plasminogen Activator ◽  
Urokinase Plasminogen Activator ◽  
Plasminogen Activator Inhibitors ◽  
Activator Protein ◽  
Type 3

The complex between urokinase plasminogen activator and its type-1 inhibitor in breast cancer extracts quantitated by ELISA

1997 ◽  
Vol 203 (1) ◽  
pp. 55-65 ◽  
Author(s):  
Anders N Pedersen ◽  
Gunilla Høyer-Hansen ◽  
Nils Brünner ◽  
Gary M Clark ◽  
Birthe Larsen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Plasminogen Activator ◽  
Urokinase Plasminogen Activator

Differential expression of plasminogen activators and their inhibitors in an organotypic skin coculture system

1993 ◽  
Vol 106 (1) ◽  
pp. 45-53 ◽  
Author(s):  
C.S. Chen ◽  
B. Lyons-Giordano ◽  
G.S. Lazarus ◽  
P.J. Jensen
Keyword(s):  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Urokinase Plasminogen Activator ◽  
Basal Cells ◽  
Type Plasminogen Activator ◽  
Inhibitor Type ◽  
Activator Inhibitor Type ◽  
Activator Inhibitor

Using immunohistochemistry and in situ hybridization, we have characterized the expression and localization of components of the plasminogen activator proteolytic cascade in an organotypic coculture system which consists of a “dermal” portion (human dermal fibroblasts throughout a collagen matrix) and a stratified, well-differentiated epidermal portion. Specifically, the following components were examined: the enzymes urokinase-type plasminogen activator and tissue-type plasminogen activator and their type 1 and type 2 inhibitors. Urokinase plasminogen activator mRNA and antigen were found predominantly in the least differentiated, basal keratinocytes; in some fields there was also faint deposition of antigen beneath the basal cells. The distribution of plasminogen activator inhibitor type 1 was similar to that of urokinase, except that inhibitor type 1 antigen deposition beneath the basal cells appeared more intense and uniform. In contrast to the results with urokinase plasminogen activator and inhibitor type 1, tissue plasminogen activator mRNA and antigen were localized focally in the suprabasal, i.e. more differentiated, keratinocytes. Plasminogen activator inhibitor type 2 mRNA and antigen were detected in most epidermal layers, but were more intense suprabasally and often spared the basal layer. These studies demonstrate that the same type of cell, i.e. the keratinocyte, can express different components of the plasminogen activator cascade depending on its state of differentiation. The change in expression of plasminogen activator cascade components with keratinocyte differentiation suggests distinct epidermal functions for these components, related to cell-matrix interaction and epidermal differentiation.

Prognostic Value of Plasminogen Activator Inhibitors in Breast Cancer

2002 ◽  
Vol 17 (2) ◽  
pp. 96-103 ◽  
Author(s):  
S. Borstnar ◽  
I. Vrhovec ◽  
T. Cufer
Keyword(s):  
Breast Cancer ◽  
Plasminogen Activator ◽  
Prognostic Value ◽  
Cox Model ◽  
Univariate Analysis ◽  
Lymph Node Status ◽  
Enzyme Linked Immunosorbent Assay ◽  
Plasminogen Activator Inhibitors ◽  
Increased Risk ◽  
Pai 1

The prognosis of cancer is primarily dependent on its potential to invade and metastasize. Data from both pre-clinical and clinical studies strongly suggest that serine proteases, as well as their inhibitors and receptor, play a central role in the processes leading to metastasis. We therefore investigated the prognostic value of plasminogen activator inhibitors type 1 (PAI-1) and type 2 (PAI-2) and the combination of both inhibitors in 332 patients with operable breast cancer. PAI-1 and PAI-2 content was measured in the primary tumor cytosols using an enzyme-linked immunosorbent assay. For PAI-1 the median value (3.9 ng/mg protein) was used as cutoff, while the optimized cutoff for PAI-2 (6.5 ng/mg protein) was obtained using the log-rank statistic. After a median follow-up of 46 months 96 (29%) patients relapsed. In univariate analysis patients with a high PAI-1 or a low PAI-2 content had an increased risk of relapse. The difference was statistically significant for PAI-1 (p<0.0001) and almost statistically significant for PAI-2 (p=0.057). Stage, tumor size, differentiation grade, lymph node status and hormone receptor status also showed significant univariate impact on disease-free survival (DFS). In multivariate analysis (Cox model) PAI-1 (p<0.0001, RR=2.78), PAI-2 (p=0.0075, RR=2.17), UICC stage (p=0.0014, RR=2.2), differentiation grade (p=0.0097, RR=1.91) and nodal status (p<0.0001, RR=2.9) retained their significance. When both inhibitors were combined the worst prognosis was observed in patients with simultaneous high PAI-1 and low PAI-2 levels, whereas low PAI-1 in combination with high PAI-2 values indicated a very favorable prognosis. In conclusion, our study showed that both PAI-1 and PAI-2 had independent prognostic value in breast cancer. Combination of both inhibitors further improved the differentiation of patients with respect to prognosis.

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