Aldehyde dehydrogenase activity selects for the holoclone phenotype in prostate cancer cells
2011
Doherty, R.E. | Haywood-Small, S.L. | Sisley, K. | Cross, N.A.
Aldehyde dehydrogenase 1 (ALDH) activity is considered to be a marker of cancer stem cells (CSCs) in many tumour models, since these cells are more proliferative and tumourigenic than ALDHᴸᵒ cells in experimental models. However it is unclear whether all CSC-like cells are within the ALDHᴴⁱ population, or whether all ALDHᴴⁱ cells are highly proliferative and tumourigenic. The ability to establish a stem cell hierarchy in vitro, whereby sub-populations of cells have differing proliferative and differentiation capacities, is an alternate indication of the presence of stem cell-like populations within cell lines. In this study, we have examined the interaction between ALDH status and the ability to establish a stem cell hierarchy in PC3 prostate cancer cells. We demonstrate that PC3 cells contain a stem cell hierarchy, and isolation of ALDHᴴⁱ cells enriches for the most primitive holoclone population, however holoclone formation is not restricted to ALDHᴴⁱ cells. In addition, we show that ALDH activity undergoes phenotypic plasticity, since the ALDHᴸᵒ population can develop ALDHᴴⁱ populations comparable to parental cells within 2weeks in culture. Furthermore, we show that the majority of ALDHᴴⁱ cells are found within the least primitive paraclone population, which is circumvented by culturing PC3 cells as spheroids in defined medium favouring stem cell characteristics. Although ALDHᴴⁱ status enriches for holoclone formation, this activity may be mediated by a minority of ALDHᴴⁱ cells.
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