BACKGROUND: In the adult human prostate CD133 expression is thought to mark rare prostate epithelial stem cells and malignant tumor stem/initiating cells.
Such putative stem cell populations are thought to proliferate slowly, but possess unlimited proliferative potential. Based on this, we hypothesized that CD133pos prostate cancer cells proliferate slower than CD133neg cells.
METHODS: Human prostate cancer cell lines were analyzed for CD133 expression and DNA content using flow cytometry. Rates of cell division and DNA synthesis were determined using CFSE cell tracing and BrdU uptake, respectively. Changes in cell cycle distribution and the percentage of CD133pos cells were assayed under conditions of different cell density and AR-pathway modulation. Lastly, we over-expressed lentiviral CD133 to measure whether CD133 regulates the cell cycle.
RESULTS: The cell cycle distribution differs between CD133pos and CD133neg cells in all three human prostate cancer cell lines studied. CD133pos cells have a greater proportion of cells in G2 and proliferate faster than CD133neg cells. High cell density increases the percentage of CD133pos cells without changing CD133pos cell cycle progression. Treatment with the AR agonist R1881, or the anti-androgen MDV3100, significantly changed the percentage and proliferation of CD133pos cells. Finally, ectopic over-expression of CD133 had no effect on cell cycle progression.
CONCLUSIONS: Contrary to our hypothesis, we demonstrate that CD133pos cells proliferate faster than CD133neg cells. This association of CD133 expression with increased cell proliferation is not directly mediated by CD133, suggesting that surface CD133 is a downstream target gene of an undefined pathway controlling cell proliferation.
Written by:
Reyes EE, Kunovac SK, Duggan R, Kregel S, Griend DJ. Are you the author?
Committee on Immunology, The University of Chicago, Chicago, Illinois.
Reference: Prostate. 2012 Nov 8. Epub ahead of print.
doi: 10.1002/pros.22616
PubMed Abstract
PMID: 23138940
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