Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, P.R. China.
Oncol Rep. 2014 Jan;31(1):79-86. doi: 10.3892/or.2013.2799. Epub 2013 Oct 18.
Lung cancer was the most commonly diagnosed cancer in 2008 worldwide. The level of fibulin-3 expression was found to be decreased in many cancer types due to aberrant promoter methylation and is correlated with poor survival of patients. However, the role of fibulin-3 and which form of fibulin-3 is expressed in lung cancer cells remain unclear. Therefore, pathologic and functional studies were carried out to determine the role of fibulin-3 in suppressing lung cancer both in vivo and in vitro. In the present study, we found that the levels of fibulin-3 mRNA and protein were lower in cancer tissues than in normal tissues. Downregulation of fibulin-3 mRNA in tumor tissues was associated with an increase in fibulin-3 promoter methylation. Circulating fibulin-3 was significantly associated with tumor progression, survival rate of lung cancer patients, and the number of circulating tumor cells (CTCs). To examine the effects of exogenous expression of fibulin-3 in vitro, lung cancer A549 cells were transfected with the pEGFP-C1-fibulin-3 expression vector. Relative to the untreated cells, fibulin-3-expressing cells exhibited lower proliferation and mobility as determined by MTT and Transwell assays, respectively. To conclude, our results suggest that fibulin-3 negatively modulates the invasiveness of lung cancer cells via regulation of p38-MAPK and MMP-2/9.
2008 年，肺癌是全球最常见的癌症。由于启动子甲基化异常，许多癌症类型中纤维连接蛋白-3 的表达水平降低，并且与患者的生存不良相关。然而，纤维连接蛋白-3 的作用以及哪种形式的纤维连接蛋白-3 在肺癌细胞中表达仍不清楚。因此，进行了病理和功能研究，以确定纤维连接蛋白-3 在体内和体外抑制肺癌的作用。在本研究中，我们发现纤维连接蛋白-3 mRNA 和蛋白在癌组织中的水平低于正常组织。肿瘤组织中纤维连接蛋白-3 mRNA 的下调与纤维连接蛋白-3 启动子甲基化的增加有关。循环纤维连接蛋白-3 与肿瘤进展、肺癌患者的生存率和循环肿瘤细胞（CTC）的数量显著相关。为了检验体外外源性表达纤维连接蛋白-3 的效果，我们用 pEGFP-C1-纤维连接蛋白-3 表达载体转染肺癌 A549 细胞。与未处理的细胞相比，纤维连接蛋白-3 表达细胞的增殖和迁移能力分别通过 MTT 和 Transwell 测定明显降低。总之，我们的结果表明，纤维连接蛋白-3 通过调节 p38-MAPK 和 MMP-2/9 负调控肺癌细胞的侵袭性。
