Why does the prostate enlarge with age? Scientists discover unusual cells hiding in one key region

Scientists have discovered a unique cell type within the prostate that may hold the key to understanding why the prostate enlarges as men age, which might provide some insight into one of the most frequent diseases seen in aging males.

The finding by scientists at Johns Hopkins University might provide an answer to a medical puzzle that has been troubling scientists for a long time: what makes the prostate enlarge in a specific area rather than the whole prostate?

According to a study published in The Journal of Pathology, scientists found a population of cells known as WIF1-positive basal cells, which were in abundance in the part of the prostate where benign enlargement takes place. The findings suggest these cells may contribute to the biological changes associated with benign prostatic hyperplasia (BPH), although their precise role remains unconfirmed.

What is benign prostatic hyperplasia?

The prostate is a small gland located near the bottom of the bladder in males. The gland creates fluid that becomes part of the male's semen and surrounds the urethra, the tube that carries urine out of the body.

The prostate may enlarge with time in older males. When the enlargement puts pressure on the urethra, it may become narrowed, which makes urination a troublesome experience.

According to the US National Institute of Diabetes and Digestive and Kidney Diseases, BPH is estimated to affect 29% to 33% of men who are 65 years old and more. Its symptoms include frequent urination, waking up at night to urinate, a weak urine flow and inability to completely empty the bladder.

Benign Prostatic Hyperplasia is not the same as prostate cancer. In BPH there is an excess of the number of cells inside the prostate, and not necessarily their size. Though hormonal changes, inflammation and cell growth are linked to the disease, its exact causes are still unknown by science.

Why does prostate enlargement occur in one region?

The prostate contains several anatomical regions, including the peripheral, central and transition zones. BPH develops predominantly in the transition zone, which surrounds the urethra. Most prostate cancers, meanwhile, originate in the peripheral zone.

This difference has puzzled researchers for years. If aging affects the prostate as a whole, why does noncancerous growth concentrate in one area?

The Johns Hopkins study offers a possible explanation by identifying a cell population that is unusually abundant in the transition zone.

How researchers identified the unusual cells

The research team studied tissue samples obtained from the prostates of 10 patients who underwent surgery due to prostate cancer. Tissue samples were taken from the three zones of the prostate gland.

With the help of single-cell RNA sequencing, the team studied the activity of more than 129,000 individual cells. Single-cell RNA sequencing enables scientists to study what genes are expressed in particular cells and what functions they may have.

The analysis revealed a distinct group of basal cells that produced high levels of a gene called WIF1. Basal cells form part of the prostate's epithelial lining.

It was found that these WIF1-positive cells are abundant in the transition zone of the prostate and rare in other zones. Using publicly available data sources, the researchers found out that the enlarged prostate contains an increased number of these cells.

It appears that these cells play some role in the formation of the biological microenvironment that makes the transition zone more susceptible to BPH. However, the results of the study do not prove that these cells trigger the development of prostate enlargement.

How could these cells contribute to prostate growth?

The authors found that the WIF1-positive basal cells had gene expression profiles that were related to hormone responses, cell growth, and tissue remodelling.

One of these processes is the epithelial-stromal remodelling. There are both epithelial cells and stromal tissue in the prostate, including connective tissue and smooth muscle cells. These various cells interact with each other and coordinate the structure of the gland.

Alterations in these interactions can result in abnormal tissue growth.

Computational analyses suggested that WIF1-positive basal cells may communicate with neighbouring epithelial cells through signalling pathways, although the effects of these interactions remain to be confirmed experimentally.

Some of the genes were also found to be involved in the reaction to androgens, which are a class of hormones including testosterone that regulate the function of the prostate.

The study did not establish a treatment targeting these cells, and further research is needed before the discovery can influence clinical care.

The relatively small initial sample, comprising tissue from 10 men undergoing prostate cancer surgery, is also an important limitation.