Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an, China.
People's Liberation Army 88 Hospital, Tai'an, China.
Cancer Gene Ther. 2014 Apr;21(4):150-7. doi: 10.1038/cgt.2014.10. Epub 2014 Apr 11.
37-kDa laminin receptor precursor (37LRP) has a crucial role in migration of some human cancers. Epithelial-to-mesenchymal transition (EMT) has received much attention in invasion and metastasis of lung cancer. Nevertheless, the role of 37LRP is not entirely clear in EMT promotion of lung cancer at present. In this study, we firstly examined the possible role of 37LRP in the invasiveness and metastasis process of lung cancer using immunohistochemistry of 80 lung adenocarcinoma cases, western blot and real-time PCR of 12 fresh lung adenocarcinoma tissues. The results showed that 37LRP significantly correlated with clinical stage and were highly expressed in metastatic lung adenocarcinomas compared with nonmetastatic ones. In vitro, we observed that 37LRP significantly increased the adhesive, invasive and metastatic abilities of human lung adenocarcinoma cell lines A549 by 37LRP-lentivirus interference. Furthermore, inoculation of A549 cells transduced with 37LRP-lentivirus in nude mice resulted in multi-metastases including the lung. In addition, western blotting and immunofluorescence were used to detect the significant difference in expression of E-cadherin and fibronectin in A549 by 37LRP-lentivirus interference compared with 37LRP-small interference RNA-lentivirus interference in vitro and vivo. The data indicated that A549 cells of epithelial cell characteristics might be induced to undergo EMT by 37LRP. A549 cells transduced with 37LRP-lentivirus showed marked morphological changes, accompanied by the decrease of epithelial marker E-cadherin and the increase of mesenchymal marker fibronectin. These results indicated that 37LRP may promote lung adenocarcinoma invasion and metastasis via the mechanism of EMT.
37kDa 层粘连蛋白受体前体(37LRP)在某些人类癌症的迁移中起着至关重要的作用。上皮-间质转化(EMT)在肺癌的侵袭和转移中受到了广泛关注。然而,目前 37LRP 在 EMT 促进肺癌中的作用尚不完全清楚。在这项研究中,我们首先使用 80 例肺腺癌病例的免疫组织化学、12 例新鲜肺腺癌组织的 Western blot 和实时 PCR 检测了 37LRP 在肺癌侵袭和转移过程中的可能作用。结果表明,37LRP 与临床分期显著相关,与非转移性肺腺癌相比,转移性肺腺癌中 37LRP 表达水平较高。在体外,我们观察到 37LRP 通过慢病毒干扰显著增加了人肺腺癌细胞系 A549 的黏附、侵袭和转移能力。此外,裸鼠接种转染 37LRP 慢病毒的 A549 细胞导致包括肺部在内的多处转移。此外,Western blot 和免疫荧光检测结果表明,与 37LRP-siRNA 慢病毒干扰相比,37LRP 慢病毒干扰在体外和体内均导致 A549 中 E-钙黏蛋白和纤维连接蛋白表达的显著差异。这些数据表明,37LRP 可能通过 EMT 诱导 A549 上皮细胞特性的细胞发生 EMT。转染 37LRP 慢病毒的 A549 细胞表现出明显的形态变化,伴随着上皮标志物 E-钙黏蛋白的减少和间充质标志物纤维连接蛋白的增加。这些结果表明,37LRP 可能通过 EMT 机制促进肺腺癌的侵袭和转移。