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Published on: October 24, 2019
Primary BPH Stromal Cell Cultures Exhibit Heightened Androgen-Responsiveness
Wei Chen1, Fulu Dong1, Mohammad Reza Askarpour1
1Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Background:
Benign prostatic hyperplasia (BPH) is the most common disease in aging males. BPH growth is androgen-dependent, and it appears that androgens preferentially stimulate the growth of BPH as compared to normal prostate. The mechanism of preferential androgen stimulation of BPH growth is not clear. Our previous studies suggest that primary BPH stromal cells, but not the paired normal adjacent prostate (NAP) stromal cells from the same patients, could stimulate prostatic epithelial cell proliferation in 3D co-culture. However, whether androgen regulation of prostatic stromal cells is altered in BPH nodules is not clear.
Methods:
Paired BPH and NAP primary stromal cells were prepared from the same patients. Early passage paired BPH and NAP primary cells were treated with androgens and/or antiandrogens for RNA-seq analysis. RNA-seq data were analyzed using principal component analysis (PCA) and functional enrichment analysis. Conditioned medium of the paired BPH and NAP primary cells in the presence or absence of androgens were used in three-dimensional (3D) culture of benign prostatic epithelial cells.
Results:
RNA-seq data analysis suggests that androgen-induced gene expression in BPH primary stromal cells is heightened compared to paired NAP stromal cells. AR activation in BPH stromal cells appears to enhance cellular motility, vascular and extracellular matrix remodeling, and paracrine signaling, while simultaneously modulating cell cycle and metabolic processes. Compared to regular BPH stromal conditioned medium, conditioned medium of androgen-stimulated BPH stromal cells further enhanced prostatic epithelial cell proliferation in 3D culture. In contrast, medium of NAP stromal cell culture conditioned in the presence of androgen had no significant effect on prostatic epithelial cell proliferation in 3D culture.
Conclusions:
Our findings suggest that androgen stimulation of prostatic epithelial cell growth via paracrine prostatic stromal signaling is enhanced in BPH and is associated with heightened androgen-responsiveness of BPH stromal cells.
