Growth kinetics of CD133-positive prostate cancer cells
Article first published online: 8 NOV 2012
Copyright © 2012 Wiley Periodicals, Inc.
Volume 73, Issue 7, pages 724–733, May 2013
How to Cite
Reyes, E. E., Kunovac, S. K., Duggan, R., Kregel, S. and Griend, D. J. V. (2013), Growth kinetics of CD133-positive prostate cancer cells. Prostate, 73: 724–733. doi: 10.1002/pros.22616
- Issue published online: 15 APR 2013
- Article first published online: 8 NOV 2012
- Manuscript Accepted: 15 OCT 2012
- Manuscript Received: 21 JUN 2012
- The University of Chicago, Department of Surgery, The Section of Urology
- The University of Chicago Comprehensive Cancer Center (UCCCC)
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University and the Cancer Research Center of the University of Chicago. Grant Number: NCI P50 CA090386
- The Cancer Research Foundation
- The Brinson Foundation
- The Alvin Baum Family Fund
- The University of Chicago Cancer Research Foundation Women's Board
- HHMI: Med-into-Grad Fellowship. Grant Number: 56006772
- Cancer Biology Training Grant. Grant Number: T32-CA09594
- Immunology Training Grant. Grant Number: AI07090-31
- androgen receptor;
- prostate cancer;
- cancer stem cell;
- cell cycle;
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.
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.
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.
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. Prostate 73: 724–733, 2013. © 2012 Wiley Periodicals, Inc.