Decrease in stromal androgen receptor associates with androgen-independent disease and promotes prostate cancer cell...

Area of Science:

• Oncology
• Molecular Biology
• Urology

Background:

• Androgen receptor (AR) is crucial in prostate cancer, but its role in stromal cells is understudied compared to epithelial cells.
• Prostate cancer research predominantly focuses on AR in malignant epithelial cells, overlooking stromal contributions.
• Stromal AR's function in both androgen-dependent and -independent prostate cancer warrants investigation.

Purpose of the Study:

• To investigate the levels and function of stromal AR in prostate cancer growth and invasion.
• To determine the impact of stromal AR expression on prostate cancer progression in vitro and in vivo.
• To explore the therapeutic potential of targeting stromal AR in hormone-refractory prostate cancer.

Main Methods:

• Analysis of stromal AR levels in prostate cancer tissues.
• Co-culture experiments using AR-positive and AR-negative human prostate stromal cell lines with prostate cancer cells.
• In vivo tumor growth assays using co-injected stromal and PC3 epithelial cells in nude mice.
• In vitro invasion assays to assess the effect of stromal AR on cancer cell invasion.

Main Results:

• Stromal AR levels were decreased in cancerous tissue, particularly in androgen-independent prostate cancer.
• AR-negative stromal cells promoted prostate cancer cell proliferation in vitro and enhanced tumor growth in vivo.
• AR-expressing stromal cells suppressed prostate cancer growth both in vitro and in vivo.
• Stromal cells lacking AR significantly increased cancer cell invasion, while AR-expressing stromal cells reduced invasion.

Conclusions:

• Stromal AR plays a critical negative regulatory role in prostate cancer growth and invasion.
• Decreased stromal AR expression may contribute to prostate cancer progression and therapeutic resistance.
• Reactivation of stromal AR presents a novel therapeutic strategy for hormone-refractory prostate cancer.