Scientists have discovered a distinct subtype of cells in the prostate, which could help solve the mystery of why the gland enlarges with age.
This natural phenomenon is called benign prostatic hyperplasia (BPH) and tends to occur in only one area of the prostate.
But scientists still don’t understand why.
Now, researchers at Johns Hopkins University have discovered a possible culprit hiding around the urethra.
Using single-cell RNA sequencing, the team identified a population of prostate cells that were particularly abundant in this region, particularly in cases of BPH.
The results are published in The pathology journal.
“Although BPH affects millions of men worldwide, scientists still do not understand why it develops primarily in a region of the prostate known as the transition zone, while other regions of the gland remain relatively unaffected,” says lead author Vasan Yegnasubramanian.
The transition zone is the part of the prostate that surrounds the urethra.
If this area enlarges with age, it can narrow the passage, making urination slower and more sporadic.
It’s the most common prostate problem in men over 50, and while changes in hormone levels, inflammation, and cell growth likely play a role, no one really knows why, on a cellular level, BPH occurs.
Urologist Charles Welliver of Albany Medical College was not involved in the recent study, but in an interview for the Urology Care Foundation podcast in August, he explained that BPH is not caused by swelling.
“Benign prostatic hyperplasia is simply an increase in the number of cells in the prostate,” Welliver said.
“So the cells are not getting bigger, their numbers are increasing.”
Scientists now believe they have discovered which units could be responsible for this cellular surge.
Johns Hopkins researchers analyzed noncancerous prostate tissue from 10 men with prostate cancer.
The samples came from the three main areas of the prostate, and the researchers carefully analyzed which genes were turned on or off in almost 130,000 individual cells.
In transition zone tissue and BPH samples, researchers discovered a distinct cell population, rare in other parts of the prostate.
These cells are a subtype of basal cells called WIF1+, and they are transcriptionally and anatomically distinct from the rest of their family members.
Scientists say they have a unique gene expression profile, and RNA sequencing and staining show they are significantly enriched in the transition zone of the human prostate.
Certain genes associated with WIF1+ cells respond to androgens such as testosterone and are involved in signaling pathways that influence prostate growth and development.
“Together,” the authors write, “the molecular signature, zonal distribution, and pathway enrichment suggest that WIF1+ basal cells enriched in transition zones may contribute to BPH pathogenesis by promoting epithelial and stromal remodeling.”
Researchers also believe that by dampening inflammation and initiating a growth signaling pathway called WNT, these cells could help explain why prostate cancer appears less often in the transition zone.
“The analysis revealed that these cells possess molecular features associated with tissue remodeling that could contribute to prostate enlargement as well as an ability to communicate with neighboring cells, suggesting that they could help establish the unique biological environment of the transition zone,” explains first author Rulin Wang.
When Wang and his colleagues analyzed publicly available datasets, they found more evidence to support their results.
Hypertrophied prostate tissues were enriched in WIF1+ basal cells.
The genetic signature of these abundant basal cells was also markedly altered.
Wang says this raises the possibility that these cells “contribute to regional processes that make the transition zone particularly susceptible to BPH.”
For now, it’s just a hypothesis, but it’s one that Wang and colleagues say merits further investigation.
Future studies, for example, could examine the functional roles of WIF1+ basal cells in the development of prostate hypertrophy.
If these cells actually play a direct role in BPH, they could become future therapeutic targets.
The research was published in The pathology journal.
This article was fact-checked by Rebecca Dyer and edited by Rebecca Dyer. Although we are proud of our process, we are only human. If you spot an error, please let us know.
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