Cui Yeting, Li Jiapeng, Liu Xiyu, Gu Lixing, Lyu Mengqing, Zhou Jingjiao, Zhang Xiaoyu, Liu Yu, Zhu Haichuan, Zhang Tongcun, Sun Fan
College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan 430065, China.
Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan 430065, China.
Cancers (Basel). 2022 Aug 25;14(17):4121. doi: 10.3390/cancers14174121.
Although great progress has been achieved in cancer treatment in the past decades, lung cancer remains the leading cause of cancer death, which is partially caused by the fact that most lung cancers are diagnosed at advanced stages. To improve the sensitivity and specificity of lung cancer diagnosis, the underlying mechanisms of current diagnosis methods are in urgent need to be explored. Herein, we find that the expression of EpCAM, the widely used molecular marker for tumor cell characterization and isolation, is strongly upregulated in primary lung tumors, which is caused by both gene amplification and promoter hypomethylation. In contrast, EpCAM expression is severely repressed in metastatic lung tumors, which can be reversed by epigenetic drugs, DNMT inhibitor 5-aza-dC and HDAC inhibitor MS-275. Moreover, tumor-associated macrophages (TAMs) impede EpCAM expression probably through TGFβ-induced EMT signaling. These findings unveil the dynamic expression patterns of EpCAM and differential roles of epigenetic modification in EpCAM expression in primary and metastatic lung tumors, providing novel insights into tumor cell isolation and lung cancer diagnosis.
尽管在过去几十年中癌症治疗取得了巨大进展，但肺癌仍然是癌症死亡的主要原因，部分原因是大多数肺癌在晚期才被诊断出来。为了提高肺癌诊断的敏感性和特异性，迫切需要探索当前诊断方法的潜在机制。在此，我们发现EpCAM（一种广泛用于肿瘤细胞表征和分离的分子标志物）在原发性肺肿瘤中表达强烈上调，这是由基因扩增和启动子低甲基化共同引起的。相反，EpCAM在转移性肺肿瘤中表达受到严重抑制，这可以通过表观遗传药物、DNA甲基转移酶抑制剂5-aza-dC和组蛋白去乙酰化酶抑制剂MS-275来逆转。此外，肿瘤相关巨噬细胞（TAM）可能通过TGFβ诱导的EMT信号传导阻碍EpCAM表达。这些发现揭示了EpCAM的动态表达模式以及表观遗传修饰在原发性和转移性肺肿瘤中EpCAM表达中的不同作用，为肿瘤细胞分离和肺癌诊断提供了新的见解。
