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

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.