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The Proportion of ALDEFLUOR-Positive Cancer Stem Cells Changes with Cell Culture Density Due to the Expression of Different ALDH Isoforms
Author(s) -
Lynn M. Opdenaker,
Shirin Modarai,
Bruce M. Boman
Publication year - 2015
Publication title -
cancer studies and molecular medicine
Language(s) - English
Resource type - Journals
ISSN - 2377-1518
DOI - 10.17140/csmmoj-2-113
Subject(s) - cancer stem cell , stem cell , aldehyde dehydrogenase , gene isoform , population , cell culture , cell , biology , cancer research , cell growth , chemistry , microbiology and biotechnology , biochemistry , enzyme , genetics , medicine , gene , environmental health
A significant number of discrepancies exist within the literature regarding ALDEFLUOR-positive stem cell populations in cell lines. We hypothesized that these inconsistencies resulted from differences in culture conditions, particularly cell density. We cultured several colon cancer cell lines (N=8) at high and low densities and found a significant decrease in ALDEFLUOR-positive cell populations at high density. However, we found no changes in the CD166-positive stem cell population, self-renewal, or cell cycle distribution of cells cultured at different densities. Interestingly, when we sorted both ALDEFLUOR positive and negative populations from the different density cultures, we identified a significant number of Aldehyde dehydrogenase (ALDH) isoforms whose expression was decreased in ALDEFLUOR-positive stem cells cultured at high density. This novel finding suggests that multiple ALDH isoforms contribute to ALDEFLUOR activity in colon cancer stem cells and decreases in ALDEFLUOR-positive stem cells at high cell density are due to decreased expression of multiple ALDH isoforms. Thus, designing therapeutics to target ALDEFLUOR-positive cancer stem cells may require inhibition of multiple ALDH isoforms.

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