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

被引:34
作者
de Witte, JH
Foekens, JA
Brünner, N
Heuvel, JJTM
van Tienoven, TH
Look, MP
Klijn, JGM
Geurts-Moespot, A
Grebenchtchikov, N
Benraad, TJ
Sweep, CGJ [1 ]
机构
[1] Univ Med Ctr Nijmegen, Dept Chem Endocrinol, Nijmegen, Netherlands
[2] Rotterdam Canc Inst, Daniel den Hoed Klin, Dept Med Oncol, Div Endocrine Oncol, Rotterdam, Netherlands
[3] Univ Rotterdam Hosp, Rotterdam, Netherlands
[4] Rigshosp, Finsen Lab, DK-2100 Copenhagen, Denmark
关键词
D O I
10.1054/bjoc.2001.1867
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. (C) 2001 Cancer Research Campaign http://www.bjcancer.com.
引用
收藏
页码:85 / 92
页数:8
相关论文
共 41 条
[1]   PLASMINOGEN-ACTIVATOR INHIBITORS - HORMONALLY REGULATED SERPINS [J].
ANDREASEN, PA ;
GEORG, B ;
LUND, LR ;
RICCIO, A ;
STACEY, SN .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 1990, 68 (01) :1-19
[2]  
Andreasen PA, 1997, INT J CANCER, V72, P1, DOI 10.1002/(SICI)1097-0215(19970703)72:1<1::AID-IJC1>3.0.CO
[3]  
2-Z
[4]   Domain interplay in the urokinase receptor - Requirement for the third domain in high affinity ligand binding and demonstration of ligand contact sites in distinct receptor domains [J].
Behrendt, N ;
Ronne, E ;
Dano, K .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (37) :22885-22894
[5]  
BEHRENDT N, 1995, BIOL CHEM H-S, V376, P269
[6]   Dissemination risk index based on plasminogen activator system components in primary breast cancer [J].
Bouchet, C ;
Hacène, K ;
Martin, PM ;
Becette, V ;
Tubiana-Hulin, M ;
Lasry, S ;
Oglobine, J ;
Spyratos, F .
JOURNAL OF CLINICAL ONCOLOGY, 1999, 17 (10) :3048-3057
[7]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[8]   Plasminogen activators, integrins, and the coordinated regulation of cell adhesion and migration [J].
Chapman, HA .
CURRENT OPINION IN CELL BIOLOGY, 1997, 9 (05) :714-724
[9]   PLASMINOGEN ACTIVATORS, TISSUE DEGRADATION, AND CANCER [J].
DANO, K ;
ANDREASEN, PA ;
GRONDAHLHANSEN, J ;
KRISTENSEN, P ;
NIELSEN, LS ;
SKRIVER, L .
ADVANCES IN CANCER RESEARCH, 1985, 44 :139-266
[10]  
DANO K, 1984, FIBRINOLYSIS, V8, P189