Official websites use. Share sensitive information only on official, secure websites. Androgen receptor AR is expressed in both the prostate epithelium and the prostate stroma and plays diverse roles in prostate physiology.
Although low expression of stromal AR is clinically associated with advanced cancer stage and worse outcome, whether stromal AR inhibits or promotes prostate cancer progression remains controversial. Histology analyses show that stromal AR deletion exacerbates tumor progression phenotypes in both models.
Furthermore, single-cell analyses of the tumor samples reveal that secretory luminal cells are the cell population particularly affected by stromal AR deletion, as they transition to a cellular state of potentiated PI3K-mTORC1 activities. Our results suggest that stromal AR normally inhibits prostate cancer progression by restraining secretory luminal cells and imply possible unintended negative effects of androgen deprivation therapy. Whether stromal androgen receptor AR promotes or inhibits prostate cancer progression is controversial.
Liu et al. Most prostate cancers PCas are adenocarcinomas that originate from the epithelial cells of the gland Shen and Abate-Shen, Both basal and luminal cells, the two major cell types of the prostate epithelium, can serve as cells of origin for PCa Choi et al. On the other hand, the stromal compartment, which is composed of smooth muscle cells SMCs , fibroblasts, endothelial cells, immune cells, and neurons, provides the crucial microenvironment for prostate development and cancer progression.
Classic tissue recombination experiments have demonstrated the essential role of stromal-epithelial interactions in prostate organogenesis Cunha et al. In PCa, the altered stromal microenvironment, named reactive stroma, can promote cancer progression Tuxhorn et al. For example, cancer-associated fibroblasts CAFs send paracrine signals, including growth factors and interleukins, to promote epithelial transformation Sasaki et al.
