Prostate progenitor cells proliferate in response to castration

Area of Science:

• Urology
• Cancer Biology
• Stem Cell Research

Background:

• Androgen deprivation is a primary treatment for advanced prostate cancer.
• Tumor regression is often incomplete due to androgen-independent cells, possibly resembling stem/progenitor cells.

Purpose of the Study:

• To investigate the response of slow-cycling progenitor cells in the adult mouse prostate to castration.
• To determine if prostate stem cells are affected by androgen deprivation.

Main Methods:

• Utilized BrdU and doxycycline-controlled histone-H2B GFP labeling in adult mice to track progenitor cells.
• Employed fluorescence-activated cell sorting (FACS) to identify and quantify stem cell markers (Sca-1, CD133, CD44, CD117) and androgen receptor expression.
• Administered BrdU post-castration to assess proliferation in specific cell populations.

Main Results:

• Identified a small population of slow-cycling, label-retaining epithelial cells at the duct-urethra junction, enriched for stem cell markers (4-marker cells) and androgen receptor positive.
• Castration induced proliferation and dispersal of these labeled progenitor cells.
• Post-castration, 16% of 4-marker cells showed BrdU incorporation, significantly higher than the 6% in all epithelial cells and controls.

Conclusions:

• Castration unexpectedly induces proliferation of prostate progenitor/stem cells.
• Androgen deprivation therapy may inadvertently expand prostate cancer stem cells, impacting treatment efficacy.