Androgen receptor moonlighting in the prostate cancer microenvironment

Area of Science:

• Oncology
• Molecular Biology
• Urology

Background:

• Androgen receptor (AR) signaling is crucial for prostate development and prostate cancer (PCa) progression.
• AR is expressed not only in prostate epithelial cells but also in stromal cells within the tumor microenvironment (TME).
• Decreased AR expression in the TME correlates with higher-grade and metastatic PCa, suggesting a protective role for stromal AR.

Purpose of the Study:

• To systematically review the literature on AR actions in various prostate stromal cell subsets.
• To elucidate the biological functions and consequences of AR signaling in the TME.
• To understand the role of stromal AR in PCa development and progression.

Main Methods:

• Systematic literature review.
• Analysis of pathological, genomic, and biological data.
• Focus on AR expression and function in prostate stromal cells (fibroblasts, macrophages, lymphocytes, neutrophils).

Main Results:

• AR is expressed in diverse cell types within the PCa TME.
• Stromal AR expression decreases in advanced PCa, indicating a potential tumor-suppressive role.
• The function of AR in stromal cells may differ from its role in PCa cells.

Conclusions:

• Stromal AR signaling in the TME warrants further investigation for its role in PCa.
• Understanding AR's non-classical functions in the TME is critical for developing novel therapeutic strategies.
• Further research is needed to fully comprehend the biological actions of AR in prostate stromal cells and their impact on cancer progression.