School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
Division of Trauma, Emergency Department Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
J Chin Med Assoc. 2019 Mar;82(3):196-201. doi: 10.1097/JCMA.0000000000000056.
Lung cancer is one of the major causes of carcinoma-related deaths in the world. Importantly, lung adenocarcinoma (LAC) is the most common type with poor outcome. However, the progressive clinical phenotype and biomolecular signature of lung cancer presenting the cancer stem-like and metastatic characteristics are still unclear.
In this study, we identified CD44 marker in lung cancers. The capabilities, including tumorigenic and migration assays, were analyzed in CD44 expression and CD44 expression subgroups. Meanwhile, the potential bio-signature and properties of lung tumor stem-like cells were further studied.
The high expression of CD44 subpopulation (CD44-positive) in isolated lung cancer cells showed significantly higher abilities of tumorigenic colonies, tumor-sphere formation, and migratory properties when compared with the CD44 expression group. These subgroups of CD44-positive lung cancer cells further demonstrated the metastatic potential with epithelial-mesenchymal transition (EMT), as well as the high expression of Twist and Snail gene profile. Importantly, the overexpression of Snail with gene vector in CD44 expression cells further significantly promoted the properties of lung tumor stem-like cells.
The results of this study highlighted the role of CD44-posivite subpopulation in modulating tumor initiation and EMT-based metastatic ability of lung malignancy.
肺癌是全球癌症相关死亡的主要原因之一。重要的是,肺腺癌(LAC)是最常见的类型,预后不良。然而,具有癌症干细胞样和转移性特征的肺癌进行性临床表型和生物分子特征仍不清楚。
在本研究中,我们鉴定了肺癌中的 CD44 标志物。在 CD44 表达和 CD44 表达亚组中分析了包括致瘤和迁移测定在内的能力。同时,进一步研究了肺肿瘤干细胞样细胞的潜在生物标志物和特性。
与 CD44 表达组相比,分离的肺癌细胞中 CD44 高表达亚群(CD44 阳性)的肿瘤形成集落、肿瘤球形成和迁移特性能力显著更高。这些 CD44 阳性肺癌细胞亚群进一步表现出具有上皮-间充质转化(EMT)的转移潜力,以及 Twist 和 Snail 基因谱的高表达。重要的是,用基因载体过表达 CD44 表达细胞中的 Snail 进一步显著促进了肺肿瘤干细胞样细胞的特性。
本研究的结果强调了 CD44-posivite 亚群在调节肿瘤起始和 EMT 为基础的肺癌恶性肿瘤转移能力中的作用。