Study of Prostate Tissue Regeneration Could Lead to Prostate Cancer Prevention

This year, the American Cancer Society estimates around 191,000 American men will discover they have prostate cancer. This slow-growing cancer is the second most common cancer found in men after skin cancer and is second only to lung cancer in terms of cancer death. According to the ACS, about one in every nine men will experience prostate cancer at some point in their lifetimes.

It’s clear that prostate cancer is a serious issue for American men. As a result, researchers at the ACS, the National Cancer Institute, and other prestigious research centers across the country are continuously working to find better ways to detect, prevent, and treat this cancer. Recently, information found in a three-institution cooperative study involving flow cytometry single cell analysis has suggested that researchers may be closer to identifying a way to interfere with the way prostate cancer cells operate.

Advanced Hormone Therapy

Currently, the primary treatment for early-stage prostate cancer is either surgical removal, radiation, or both. However, if the cancer does not respond to these treatments – or if the cancer is not detected until it is too advanced for either procedure – the generally accepted next step is hormone therapy, also known as chemical castration. In some cases, too, hormone therapy can be used to reduce the size of the tumor and allow for more effective surgical removal or other therapies.

Hormone therapy involves the use of luteinizing hormone-releasing hormone (LHRH) antagonist drugs to lower testosterone levels quickly, reducing the tumor’s ability to grow. In combination with surgery, this form of chemical castration leads to prostate shrinkage and the loss of the luminal epithelial cells that line the prostate’s lumen, providing secretions and acting as androgen receptors. Now, however, researchers participating in a joint effort among the Broad Institute, MIT, and Memorial Sloan Kettering Cancer Center have found evidence that prostate regeneration may be possible.

Single Cell RNA Sequencing Leads to New Findings

After isolating nearly 13,400 individual mouse prostate cells, researchers were able to perform single cell RNA sequencing on these tissue samples. They found numerous subtypes of cells within these samples that were much more diverse than previously thought. In fact, researchers isolated sixteen non-epithelial cell clusters and six epithelial cell clusters, including clusters of luminal epithelial cells – largely considered origin cells in which prostate cancer propagates.

Since previous studies of mouse models had revealed that mice can replace lost tissue after exposure to testosterone, researchers were very interested in the genetic origins of these cell clusters and their behavior after chemical castration. Researchers utilized lineage tracking to follow the behavior of luminal cells after hormone therapy. Subsequent tissue and cell regeneration research confirmed that these luminal cells – rather than stem cells – led to prostate tissue regeneration and behaved much like liver cells and other stem cells with similar regenerative capabilities.

Researchers extended these studies to include corresponding research with human prostate samples, which included additional single-cell RNA sequencing, imaging, and organ modeling. Together, these human and mouse prostate cell studies revealed that chemical castration seems to have a “reprogramming” effect on some prostate cells. As these cells re-emerge as cell populations similar to stem cells after androgen deprivation, they could stand to regenerate lost prostate tissue.

Future Implications

For researchers involved in the study, this newly revealed information about how the prostate responds and recovers after advanced hormone therapy could lead to greater insights for prostate cancer treatment. Since cancer cells regenerate and reproduce within luminal epithelial origin cells, knowledge about this process could help researchers find ways to interfere with the malignant origin cells that cause tumors. Much more research is needed to develop an understanding about how this exact mechanism unfolds but, if it is successful, findings could lead to new, more effective prostate cancer treatments.

Such findings are positive news for those with prostate cancer. Currently, screening for prostate cancer in high risk populations is a primary way to detect it before symptoms appear. However, since it is so slow-growing, early treatment is not always effective. Attention to disrupting cancer’s mechanisms of regeneration may bring new hope to stopping prostate cancer in its tracks.