Non-small cell lung cancer stem/progenitor cells are enriched in multiple distinct phenotypic subpopulations and exhibit plasticity

被引:101
作者
Akunuru, S. [1 ,2 ]
Zhai, Q. James [3 ]
Zheng, Y. [1 ,2 ]
机构
[1] Univ Cincinnati, Div Expt Hematol & Canc Biol, Childrens Hosp Res Fdn, Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA
[2] Univ Cincinnati, Mol Dev Biol Program, Childrens Hosp Res Fdn, Cincinnati, OH 45229 USA
[3] Univ Cincinnati, Dept Pathol & Lab Med, Cincinnati, OH 45229 USA
来源
CELL DEATH & DISEASE | 2012年 / 3卷
关键词
lung cancer; cancer stem cells; Rac1; EMT; self-renewal; plasticity; STEM-CELLS; SIDE POPULATION; GROWTH; ADENOCARCINOMA; IDENTIFICATION; TRANSITION; EQUILIBRIUM; PATHWAY; TUMORS; A549;
D O I
10.1038/cddis.2012.93
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Cancer stem cells (CSCs) represent a population of cancer cells that possess unique self-renewal and differentiation characteristics required for tumorigenesis and are resistant to chemotherapy-induced apoptosis. Lung CSCs can be enriched by several markers including drug-resistant side population (SP), CD133(pos) and ALDH(high). Using human non-small cell lung adenocarcinoma cell lines and patient-derived primary tumor cells, we demonstrate that SP cells represent a subpopulation distinct from other cancer stem/progenitor cell (CS/PC) populations marked by CD133(pos) or ALDH(high). The non-CS/PCs and CS/PCs of each subpopulation are interconvertible. Epithelial-mesenchymal transition (EMT) promotes the formation of CD133(pos) and ALDH(high) CS/PC subpopulations while suppressing the SP CS/PC subpopulation. Rac1 GTPase activity is significantly increased in cells that have undergone EMT, and targeting Rac1 is effective in inhibiting the dynamic conversion of non-CS/PCs to CS/PCs, as well as the CS/PC activity. These results imply that various subpopulations of CS/PCs and non-CS/PCs may achieve a stochastic equilibrium in a defined microenvironment, and eliminating multiple subpopulations of CS/PCs and effectively blocking non-CS/PC to CS/PC transition, by an approach such as targeting Rac1, can be a more effective therapy. Cell Death and Disease (2012) 3, e352; doi:10.1038/cddis.2012.93; published online 19 July 2012
引用
收藏
页码:e352 / e352
页数:10
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