Liu Shu-Yan, Zheng Peng-Sheng
Department of Reproductive Medicine, The First Affiliated Hospital of the Medical College, Xi'an Jiaotong University, Xi'an, The People's Republic of China.
Oncotarget. 2013 Dec;4(12):2462-75. doi: 10.18632/oncotarget.1578.
High aldehyde dehydrogenase (ALDH) activity characterizes a subpopulation of cells with cancer stem cell (CSC) properties in several malignancies. To clarify whether ALDH can be used as a marker of cervical cancer stem cells (CCSCs), ALDH high and ALDH low cells were sorted from 4 cervical cancer cell lines and 5 primary tumor xenografts and examined for CSC characteristics. Here, we demonstrate that cervical cancer cells with high ALDH activity fulfill the functional criteria for CSCs: (1) ALDH high cells, unlike ALDH low cells, are highly tumorigenic in vivo; (2) ALDH high cells can give rise to both ALDH high and ALDH low cells in vitro and in vivo, thereby establishing a cellular hierarchy; and (3) ALDH high cells have enhanced self-renewal and differentiation potentials. Additionally, ALDH high cervical cancer cells are more resistant to cisplatin treatment than ALDH low cells. Finally, expression of the stem cell self-renewal-associated transcription factors OCT4, NANOG, KLF4 and BMI1 is elevated in ALDH high cervical cancer cells. Taken together, our data indicated that high ALDH activity may represent both a functional marker for CCSCs and a target for novel cervical cancer therapies.
在多种恶性肿瘤中，高醛脱氢酶（ALDH）活性是具有癌症干细胞（CSC）特性的细胞亚群的特征。为了阐明ALDH是否可作为宫颈癌干细胞（CCSC）的标志物，从4种宫颈癌细胞系和5种原发性肿瘤异种移植中分离出ALDH高表达和ALDH低表达细胞，并检测其CSC特性。在此，我们证明具有高ALDH活性的宫颈癌细胞符合CSC的功能标准：（1）与ALDH低表达细胞不同，ALDH高表达细胞在体内具有高度致瘤性；（2）ALDH高表达细胞在体外和体内均可产生ALDH高表达和ALDH低表达细胞，从而建立细胞层次结构；（3）ALDH高表达细胞具有增强的自我更新和分化潜能。此外，ALDH高表达的宫颈癌细胞比ALDH低表达细胞对顺铂治疗更具抗性。最后，干细胞自我更新相关转录因子OCT4、NANOG、KLF4和BMI1在ALDH高表达的宫颈癌细胞中表达升高。综上所述，我们的数据表明高ALDH活性可能既是CCSC的功能标志物，也是新型宫颈癌治疗的靶点。
