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

// Shu-Yan Liu 1 and Peng-Sheng Zheng 1,2 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), 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 i n 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.