摘要
目前,不断有证据证明肿瘤源自组织成体干细胞或其祖细胞的恶性转化,这些转化的干(祖)细胞称为肿瘤起始细胞(tumor-initiating cells)或肿瘤干细胞(cancer stem cells,CSC)。但肺癌CSC细胞的起源尚不清楚。该实验室曾报道人体肺腺癌中存在一类表达OCT4(octamer-binding transcription factor 4)的细支气管肺泡干细胞(bronchioalveolar stem cell,BASC)样CSC。该研究采用RNA干扰技术灭活了此类癌细胞中的锌指蛋白转录因子编码基因多形腺瘤样基因2(pleiomorphic adenoma gene-like 2,PLAGL2),证明该基因表达沉默驱使肺腺癌CSC分化形成了I型肺泡细胞(alveolartype 1 cells,AT1)样细胞并失去致瘤能力。借助基因芯片筛查技术平台,发现肺腺癌CSC具有与人体肺脏未分化干细胞和肺泡祖细胞相似的分子表型,提示此类肺干(祖)细胞可能是肺腺癌潜在的细胞起源。此外,该研究结果还揭示肺腺癌CSC的分化受TTF-1(甲状腺转录因子-1)和PLAGL2的双重调控,通过基因操作以及药理性诱导可以驱使此类癌细胞分化。这些结果为针对肺癌CSC的靶向治疗提供了新的思路。
Emerging evidence indicated that tumors originated from malignant transformation of tissue- resident stem cells and/or progenitor cells. These transformed stern/progenitor cells are named as tumor-initiating cells or cancer stem cells （CSC）. However, the potential cell origion of CSC in lung cancer remains unclear at pres- ent. We reported the existance of OCT4-expressing BASC （bronchiolaveolar stem cells）-like CSC in human lung adenocarcinoma. With the technique of RNA interfering, we inactivated the expression of PLAGL2 （pleiomorphic adenoma gene-like 2）, a gene encoding the zinc finger transcription factors, in the CSC of lung adenocarcinoma. The results demonstrated that knockdown of PLAGL2 enforced the cells to differentiate into the AT 1 （alveolar type 1） cell-like state and lost the tumorigenic ability. With the plateform of microarray （gene chip） screening, we showed that the CSC in lung adenocarcinoma shared molecular phenotypes with the undifferentiated stem cells and the alveolar progenitor cells of human lung, suggesting these primitive cells as a promising cell origion of CSC in lung adenocarcinoma. In addition, the results presented herein revealed that the differentiation of CSC in lung ad- enocarcinoma was under the dural control of TTF-1 （thyroid transcription factor-1） and PLAGL2. By gene menag- ment and pharmacolical induction, these CSCs were able to differentiate. These studies provided a novel evanue for CSC-targeted theranies in lung cancer
出处
《中国细胞生物学学报》
CAS
CSCD
北大核心
2012年第4期366-375,共10页
Chinese Journal of Cell Biology
基金
国家自然科学基金(No.30872952)
上海市科委科研基金(No.09411-961700
No.10411968600)
上海市卫生局科研基金(No.2009198)资助项目~~
