Castelló Remedios, Landete Jose M, España Francisco, Vázquez Carlos, Fuster Carlos, Almenar Sergio M, Ramón Luis A, Radtke Klaus-Peter, Estellés Amparo
Hospital Universitario La Fe, Valencia, Spain.
Thromb Res. 2007;120(5):753-62. doi: 10.1016/j.thromres.2006.12.016. Epub 2007 Jan 29.
The urokinase plasminogen activator (uPA) system has been involved in cancer cell invasion and in metastasis. uPA activity is controlled by its principal inhibitor, the PA inhibitor type-1 (PAI-1), but it can also be inhibited by PAI-3. Increased levels of uPA and PAI-1 are known to be associated with a poor prognosis in breast cancer. To our knowledge this is the first study of the expression and role of PAI-3 in human breast cancer tissue.
Protein and mRNA levels were evaluated for uPA, PAI-1 and PAI-3 in breast cancer tissues from 70 different patients. The localization of antigen and mRNA of these proteins was studied by immunohistochemistry and in situ hybridization, respectively.
No significant differences were observed for PAI-3 mRNA or protein levels between the nodal status groups or the different post-surgical tumor-node-metastasis (pTNM) stages. However, uPA and PAI-1 mRNA and antigen levels significantly increased at the pTNM stage and in node-positive patients. PAI-3 antigen levels were significantly higher in early relapse-free patients, whereas PAI-1 antigen levels were significantly higher in patients who suffered a relapse. PAI-3 protein and mRNA were localized in stromal cells. PAI-1 and uPA protein were detected in cancer, endothelial and stromal cells and their mRNA mainly in stromal cells.
Our results indicate that PAI-3 is expressed in human breast cancer tissues, and that elevated levels of PAI-3 could be a positive prognostic factor in this disease. A potential mechanism for the contribution of PAI-3 to a positive long-term outcome may involve suppression of tumor invasion through protease inhibition in stroma.
尿激酶型纤溶酶原激活剂（uPA）系统与癌细胞侵袭和转移有关。uPA活性受其主要抑制剂1型PA抑制剂（PAI-1）控制，但也可被PAI-3抑制。已知uPA和PAI-1水平升高与乳腺癌预后不良有关。据我们所知，这是第一项关于PAI-3在人乳腺癌组织中的表达及作用的研究。
对70例不同患者的乳腺癌组织中uPA、PAI-1和PAI-3的蛋白质和mRNA水平进行评估。分别通过免疫组织化学和原位杂交研究这些蛋白质的抗原和mRNA定位。
在淋巴结状态组或不同的术后肿瘤-淋巴结-转移（pTNM）分期之间，未观察到PAI-3 mRNA或蛋白质水平有显著差异。然而，在pTNM分期和淋巴结阳性患者中，uPA和PAI-1 mRNA及抗原水平显著升高。早期无复发患者的PAI-3抗原水平显著更高，而复发患者的PAI-1抗原水平显著更高。PAI-3蛋白质和mRNA定位于基质细胞。PAI-1和uPA蛋白质在癌细胞、内皮细胞和基质细胞中检测到，其mRNA主要在基质细胞中。
我们的结果表明，PAI-3在人乳腺癌组织中表达，且PAI-3水平升高可能是该疾病的一个阳性预后因素。PAI-3对长期良好预后有贡献的潜在机制可能涉及通过抑制基质中的蛋白酶来抑制肿瘤侵袭。
