Oncotarget

Research Papers:

High aldehyde dehydrogenase activity identifies cancer stem cells in human cervical cancer

Shuyan Liu and Pengsheng Zheng _

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Oncotarget. 2013; 4:2462-2475. https://doi.org/10.18632/oncotarget.1578

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Abstract

Shu-Yan Liu1 and Peng-Sheng Zheng1,2

1 Department of Reproductive Medicine, The First Affiliated Hospital of the Medical College, Xi’an Jiaotong University, Xi’an, The People’s Republic of China

2S ection of Cancer Stem Cell Research, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of the People’s Republic of China, Xi’an, The People’s Republic of China

Correspondence:

Peng-Sheng Zheng, email:

Keywords: aldehyde dehydrogenase, cancer stem cells, cervical cancer, self-renewal, chemoresistance

Received: November 5, 2013 Accepted: November 23, 2013 Published: November 25, 2013

Abstract

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), ALDHhigh and ALDHlow 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) ALDHhigh cells, unlike ALDHlow cells, are highly tumorigenic in vivo; (2) ALDHhigh cells can give rise to both ALDHhigh and ALDHlow cells in vitro and in vivo, thereby establishing a cellular hierarchy; and (3) ALDHhigh cells have enhanced self-renewal and differentiation potentials. Additionally, ALDHhigh cervical cancer cells are more resistant to cisplatin treatment than ALDHlow cells. Finally, expression of the stem cell self-renewal-associated transcription factors OCT4, NANOG, KLF4 and BMI1 is elevated in ALDHhigh 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.


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