Aldehyde dehydrogenase activity selects for the holoclone phenotype in prostate cancer cells |
| |
Authors: | Doherty R E Haywood-Small S L Sisley K Cross N A |
| |
Affiliation: | aBiomedical Research Centre, Sheffield Hallam University, Sheffield S1 1WB, UK;bDepartment of Oncology, Academic Unit of Ophthalmology and Orthopties, University of Sheffield, Sheffield S10 2RX, UK |
| |
Abstract: | 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 2 weeks 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. |
| |
Keywords: | Stem cell hierarchy Aldehyde dehydrogenase Cancer stem cells Prostate cancer |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|