尿激酶型纤溶酶原激活物抑制剂1参与非小细胞肺癌的侵袭与转移  

PAI-1 involve in invasion and metastasis of non-small cell lung cancer

作　　者：刘明[1] 周承志[1] 欧阳铭[1] 

机构地区：[1]广州医科大学附属第一医院 广州呼吸疾病研究所 呼吸疾病国家重点实验室,510120

出　　处：《国际呼吸杂志》2015年第12期881-885,共5页International Journal of Respiration

基　　金：国家自然科学基金（81200050）;呼吸疾病国家重点实验室青年基金（2011-A8）;广州市属高校科研计划项目（2012C157）

摘　　要：目的：探讨尿激酶型纤溶酶原激活物抑制剂1（PAI-1）的表达与非小细胞肺癌（NSCLC）的浸润转移的关系。方法应用免疫组化的方法,观察68例 NSCLC 患者标本中 PAI-1在肺癌组织中的表达及细胞定位,分析其与肺癌病理类型、分期、转移的关系。检测 PAI-1在 NSCLC 细胞系中的表达,分析其与转移相关分子基质金属蛋白酶9的关系,观察细胞因子复合物 Cytomix（TGF-β1＋IL-1β＋IFN-γ）刺激 A549细胞后 PAI-1的变化及 PAI-1 siRNA 转染对其侵袭能力的影响。结果在 NSCLC 组织标本中,PAI-1的表达主要分布于细胞胞浆,部分可为细胞膜或细胞核,表达可见于肿瘤细胞、间质成纤维细胞、血管内皮细胞及部分巨噬细胞,阳性表达率分别为64.7%、44.1%、25.0%、22.1%（P 〈0.01）。PAI-1高表达多见于Ⅱ～Ⅲ期、有远处转移的肺癌患者。PAI-1在不同 NSCLC 细胞系具有不同的表达水平,且与转移相关蛋白基质金属蛋白酶9的表达一致。Cytomix 刺激可导致 PAI-1表达的上调,使A549细胞转分化为具有侵袭性的梭形细胞,而给予 PAI-1 siRNA 能抑制该表型的出现。结论 PAI-1在肺癌组织中高表达,提示其在肿瘤发生过程中发挥一定的作用,其不同的表达模式提示其不同的功能需要,PAI-1的表达与转移密切相关。Objective To investigate the expression and clinical significance of plasminogen activator inhibitor-1 （PAI-1 ）in non-small cell lung cancer （NSCLC）.Methods Immunohistochemistry was applied to evaluate the expression of PAI-1 protein in 68 paraffin-embedded specimens with NSCLC, the correlations of their expression to the clinicopathologic characteristics of patients were analyzed.The expression and correlations of PAI-1 and matrix metalloprotein-9,and the role of PAI-1 in cell invasion were investigated in NSCLC cell lines by cytomix （transforming growth factor-β1 ＋ interleukin-1β＋interferon-γ）stimulation and PAI-1 siRNA transfection.Results The positive rate of PAI-1 in NSCLC tumor cell,fibroblast,endothelial cell,and macrophage were 64.7%,44.1%,25.0%,and 22.1% （P 〈0.01）.Higher positive rate of PAI-1 was associated with greater metastatic ability and Ⅱ-Ⅲ stage,but not associated with age,histological type,and pathologic grade.Higher expression of PAI-1 was associated with matrix metalloprotein-9 in NSCLC cell lines.Overexpression of PAI-1 caused by cytomix showed an invasion phenotype,which could be reversed by PAI-1 siRNA transfection.Conclusions PAI-1 was up-regulated in NSCLC,and might be participated in the metastasis of NSCLC.

关 键 词：非小细胞肺癌 纤溶酶原激活物抑制剂1 侵袭与转移 

分 类 号：R782[医药卫生—口腔医学]