Scientists have discovered a cell subtype in the prostate called WIF1+ that could explain why the gland enlarges with age, a condition known as benign prostatic hyperplasia (BPH). This subtype of basal cells differs genetically and anatomically from the rest of its group, and the discovery offers a new target for treatment.
Researchers at Johns Hopkins University found a potential cellular driver of this process in the tissue surrounding the urethra. Using single-cell RNA sequencing, the team identified a population of prostate cells that is particularly abundant in this area, especially in cases of BPH. The findings were published in The Journal of Pathology, with Vasan Yegnasubramanian as the lead author.
The transition zone is the part of the prostate that surrounds the urethra. If this zone enlarges with age, it can narrow the channel, causing urination to become slower and intermittent. This is the most common prostate problem in men over 50, but the cellular mechanism behind BPH has not previously been known.
Urologist Charles Welliver from Albany Medical College, who was not involved in the study, clarified that BPH is not the result of swelling. In an interview for the Urology Care Foundation podcast in August, he stated that benign prostatic hyperplasia is simply an increase in the number of cells within the prostate, noting that the cells do not become larger, but there are more of them.
Johns Hopkins scientists analysed non-cancerous prostate tissue from 10 men who had prostate cancer. Samples were taken from the three main zones of the gland, and the researchers analysed gene activity in nearly 130,000 individual cells. In the transition zone tissues and BPH samples, they found a specific population of cells that is rare in other parts of the prostate.
These cells have a unique gene expression profile and are extremely numerous in the transition zone of the human prostate. Some genes associated with WIF1+ cells respond to androgens such as testosterone and participate in signalling pathways that affect prostate growth and development. The authors suggest that WIF1+ basal cells in the transition zone may contribute to the development of BPH because they promote tissue remodelling.
The researchers also hypothesise that these cells could explain why prostate cancer less often begins in the transition zone, as they believe the cells dampen inflammation and a growth signalling pathway known as WNT. First author Rulin Wang said the analysis revealed that these cells possess molecular features associated with tissue remodelling, which could contribute to prostate enlargement. She added that the cells have the ability to communicate with neighbouring cells, so it is presumed they help create the unique biological environment of the transition zone.
When Wang and her colleagues analysed publicly available databases, they found additional evidence for their results. Enlarged prostate tissues were rich in WIF1+ basal cells, and their genetic signature was clearly altered. Wang added that this opens the possibility that these cells contribute to local processes that make the transition zone particularly susceptible to BPH.
For now, this is only a hypothesis, but the authors believe it warrants further investigation. Future studies could examine the exact role of WIF1+ basal cells in the development of an enlarged prostate. If they are shown to have a direct role, they could become a target for the development of new drugs.
