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肿瘤干细胞(cancer stem cells,CSC)是指一类具有自我更新(self-renewal)能力的未分化细胞。在肺腺癌中,CSC的自我更新调控机制类似胚胎干细胞,即高表达OCT4、Nanog和Sox2多潜能基因,但目前对其表型特征尚存争议。该文采用成球试验(sphere-forming assay)从SPC-A1细胞株中富集CSC后进行分子表型分析。结果显示,此类肺球体细胞(pulmospheres)同时表达肺脏近端和远端呼吸上皮的多个谱系(lineage)标志,包括纤毛柱状细胞标志FoxJ1、非纤毛柱状细胞(即Clara细胞)标志CCSP、肺神经内分泌细胞标志GRP、II型肺泡细胞标志SP-C及其转录调控因子TTF-1。这些肺球体细胞也能够被3株小细胞肺癌特异性单抗(2F7、4B3和E6)所识别。通过基因沉默技术使得肺球体细胞中OCT4表达转阴后,上述标志(除E6外)均消失。研究结果揭示,肺癌CSC具有肺脏呼吸上皮多潜能细胞的表型特征。此外,初步研究结果发现,中药冬虫夏草(Hirsutella Hepialid of Cordyceps Sinensis)的被毛孢菌丝体中含有新颖抗癌成分,能够显著遏制肺球体细胞增殖,提示对其进行分离鉴定,将是研制开发肺癌CSC靶向药物的一个发展方向。
Cancer stem cells (CSC) refer to a class of undifferentiated cells with self-renewal ability. In lung adenocarcinoma, the self-renewal regulatory mechanism of CSC is similar to that of embryonic stem cells, that is, overexpressing OCT4, Nanog and Sox2 pluripotency genes. However, their phenotypic characteristics are still controversial. This article uses a sphere-forming assay to perform molecular phenotyping after enrichment of CSCs from SPC-A1 cell lines. The results showed that such pulmospheres simultaneously expressed multiple lineage markers of the lung proximal and distal respiratory epithelia, including the ciliary columnar cell marker FoxJ1, the non-ciliated columnar cell (ie Clara cell) marker CCSP, the lung Neuroendocrine cell marker GRP, type II alveolar cell marker SP-C and its transcriptional regulator TTF-1. These lung spheroplasts were also recognized by three small cell lung cancer specific monoclonal antibodies (2F7, 4B3 and E6). The above markers (except E6) disappeared after OCT4 expression was down-regulated in lung globus pallidus by gene silencing technique. The results revealed that lung cancer CSC has the phenotypic characteristics of lung epithelial cells. In addition, the preliminary study found that the Chinese herbal Cordyceps sinensis (Hirsutella Hepialid of Cordyceps Sinensis) contains a new anti-cancer components of Mycelial spores, can significantly inhibit the proliferation of lung spheroid cells, suggesting that its separation and identification will be the development of lung cancer CSC targeted drug development.