Grebenchtchikov N, Maguire T M, Riisbro R, Geurts-Moespot A, O'Donovan N, Schmitt M, McGreal G, McDermott E, O'Higgins N, Brünner N, Sweep C G J, Duffy M J
Department of Chemical Endocrinology, University Medical Centre Nijmegen, Nijmegen, The Netherlands.
Oncol Rep. 2005 Jul;14(1):235-9.
The plasminogen activator (PA) system comprises the 2 serine proteases, urokinase PA (uPA) and tissue PA (tPA), the 2 serpin inhibitors, PAI-1 and PAI-2 and the uPA receptor (uPAR; CD87). High levels of uPA, PAI-1, uPA-PAI-1 complex and uPAR in breast cancer tissue are associated with poor prognosis, while high levels of tPA or PAI-2 correlate with good prognosis. In this study, pre-operative plasma levels of uPA, PAI-1, uPAR, tPA, uPA-PAI-1 complex, and tPA-PAI-1 complex were measured in patients with benign (n=103) and malignant breast disease (n=113) by immunoenzymatic assays (ELISA). While plasma antigen levels of uPA, PAI-1, uPA-PAI-1 complex and uPAR were not significantly different in the 2 groups, antigen levels of tPA and tPA-PAI-1 complex were significantly higher in patients with breast carcinoma compared to the control group. In plasma from the breast cancer patients, uPA levels correlated weakly but significantly with those of tPA (r=0.20, p=0.035) and uPAR (r=0.208, p=0.028). tPA levels correlated strongly with tPA-PAI-1 complex (r=0.972, p=0.0001) while uPA-PAI-1 levels were significantly associated with PAI-1 levels (r=0.534, p<0.0001), tPA levels (r=0.348, p=0.0003) and tPA-PAI-1 levels (r=0.356, p=0.002). However, no significant correlation was found between plasma and tumor tissue levels of uPA, PAI-1, uPA-PAI-1 complex, tPA or tPA-PAI-1. Our findings indicate that determination of these factors in plasma do not reflect their concentration in tumor tissue. Therefore, measurement of PA components in blood cannot be recommended for assessing prognosis in breast cancer.
纤溶酶原激活物（PA）系统由2种丝氨酸蛋白酶，即尿激酶型PA（uPA）和组织型PA（tPA）、2种丝氨酸蛋白酶抑制剂，即PAI-1和PAI-2以及uPA受体（uPAR；CD87）组成。乳腺癌组织中uPA、PAI-1、uPA-PAI-1复合物和uPAR水平较高与预后不良相关，而tPA或PAI-2水平较高则与预后良好相关。在本研究中，通过免疫酶测定法（ELISA）检测了良性乳腺疾病患者（n=103）和恶性乳腺疾病患者（n=113）术前血浆中uPA、PAI-1、uPAR、tPA、uPA-PAI-1复合物和tPA-PAI-1复合物的水平。虽然两组中uPA、PAI-1、uPA-PAI-1复合物和uPAR的血浆抗原水平无显著差异，但与对照组相比，乳腺癌患者的tPA和tPA-PAI-1复合物抗原水平显著更高。在乳腺癌患者的血浆中，uPA水平与tPA水平呈弱但显著的相关性（r=0.20，p=0.035），与uPAR水平也呈弱但显著的相关性（r=0.208，p=0.028）。tPA水平与tPA-PAI-1复合物呈强相关性（r=0.972, p=0.0001），而uPA-PAI-1水平与PAI-1水平显著相关（r=0.534，p<0.0001）、与tPA水平显著相关（r=0.348，p=0.0003）以及与tPA-PAI-1水平显著相关（r=0.356，p=0.002）。然而，血浆和肿瘤组织中uPA、PAI-1、uPA-PAI-1复合物、tPA或tPA-PAI-1的水平之间未发现显著相关性。我们的研究结果表明，血浆中这些因子的测定并不能反映它们在肿瘤组织中的浓度。因此，不建议通过检测血液中的PA成分来评估乳腺癌的预后。
