Johns Hopkins Researchers Identify Cells Linked to Prostate Enlargement

Researchers at Johns Hopkins University have identified a distinct population of prostate cells that may help explain why the gland enlarges with age, a condition known as benign prostatic hyperplasia (BPH). Their findings, based on analyses of human prostate tissue, point to WIF1+ basal cells concentrated in the transition zone surrounding the urethra, where enlargement can obstruct urine flow.

BPH is a common prostate condition in men older than 50. Although hormonal changes, inflammation, and cellular growth have been linked to the condition, scientists have not established why enlargement primarily affects the transition zone while other parts of the gland remain relatively unaffected.

The Johns Hopkins team analyzed noncancerous prostate tissue from 10 men who had prostate cancer. Using single-cell RNA sequencing, the researchers examined gene activity in nearly 130,000 individual cells collected from the prostate's three major zones.

The analysis revealed a distinct population of basal cells known as WIF1+ cells. According to the researchers, these cells were substantially more abundant in the transition zone and displayed molecular characteristics that distinguished them from other basal cells.

Some genes associated with WIF1+ cells respond to androgens, including testosterone, and participate in signaling pathways involved in prostate growth and development. The researchers suggest these cellular characteristics could contribute to changes in the epithelial and stromal tissues that accompany BPH.

Senior author Vasan Yegnasubramanian described the unresolved question behind the investigation.

"Although BPH affects millions of men worldwide, scientists still do not fully 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," explained Vasan Yegnasubramanian, the study's senior author.

The transition zone surrounds the urethra, the tube that carries urine out of the body. When the prostate enlarges in this area, it can narrow the passage and make urination slower and less consistent.

The findings also provide a possible explanation for differences in cancer development across prostate regions. The researchers speculate that WIF1+ basal cells may influence inflammation and the WNT growth-signaling pathway, potentially contributing to the transition zone's distinct biological environment and its lower frequency of prostate cancer onset.

First author Rulin Wang said the cells' molecular properties could help explain their role in the tissue surrounding the urethra.

"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 they may help establish the unique biological environment of the transition zone," said Rulin Wang, the study's first author.

To assess their initial findings, Wang and colleagues examined publicly available datasets. They found that enlarged prostate tissues contained elevated proportions of WIF1+ basal cells and that the gene-expression patterns associated with these cells were distinctly altered.

Wang said the results support further investigation into the cells' potential contribution to BPH.

"Contribute to the regional processes that make the transition zone particularly susceptible to BPH," said Wang, describing the possible role of WIF1+ basal cells.

The researchers emphasized that the proposed connection remains a hypothesis rather than proof that these cells directly cause prostate enlargement. Further studies could investigate their functional role in BPH development and determine whether they might provide targets for future treatments.

Urologist Charles Welliver of Albany Medical College, who was not involved in the study, previously explained that BPH involves an increase in the number of prostate cells rather than an increase in their individual size.

"Benign prostatic hyperplasia is just an increase in the number of cells within the prostate," said Charles Welliver, a urologist at Albany Medical College.

Welliver further clarified the distinction between cell growth and cell number when discussing the condition in an interview for the Urology Care Foundation's podcast in August.

"So, the cells don't get bigger, there's an increase in the number," said Welliver.

The Johns Hopkins findings identify WIF1+ basal cells as a potential contributor to this cellular increase, but additional research is needed to establish whether the cells play a direct role in the development of BPH.