Prostate cancer is the most common type of cancer and the second largest cause of cancer-related deaths in men in the United States.
Researchers have documented the cell dynamics of prostate cancer at a single-cell resolution throughout the disease’s progression, from the early stages to the point of androgen independence, when the tumour no longer responds to hormone restriction treatment.
Their mouse study, published in eLife, shows that intermediate cells grow in prostate cancer, which correlates with treatment resistance & poor patient outcomes in humans. These cells are castration-resistant, which means they continue to grow even when testosterone is not present. This might explain why prostate cancers develop resistance to hormone-related therapy.
Patients suffering from prostate cancer may soon find relief.
Prostate cancer is the most common type of cancer and the second largest cause of cancer-related deaths in men in the United States. This is largely owing to a lack of understanding of the cellular processes behind disease development and the risk of developing castration-resistant prostate cancer (CRPC).
The prostate gland epithelium consists of two types of epithelial cells: basal cells and highly differentiated luminal cells, which form the surface of glands and organs (cells which have altered in form). Previously, a more stem-like, castration-resistant intermediate of luminal cells was hypothesised.
“According to lead author Alexandre Germanos, a PhD candidate in Molecular and Cellular Biology at the University of Washington in the US and a graduate student at the Division of Human Biology, Fred Hutchinson Cancer Research Center in the US, normal luminal cells may transform into these progenitor cells under castrate conditions. Although this has not yet been demonstrated in other CRPC models, there is evidence that these cells have a role in the early development of prostate tumours and treatment resistance in advanced malignancies.
Germanos and colleagues utilised a mouse model of CRPC to develop a ‘map of prostate cellular composition and evolution’ during the course of the disease to investigate this further.
The majority of advanced prostate cancer patients have an inactive Pten gene, which codes for a tumor-suppressing enzyme. The researchers utilised a technique known as single-cell RNA sequencing to examine the populations of epithelial and non-epithelial cell types in healthy mice versus those without Pten. They discovered many epithelial cell types in the prostates of healthy mice, including basal, luminal, and luminal progenitor cells. They discovered an increase in luminal intermediate cells in the prostates of animals missing Pten, which were likely produced from three cellular sources: basal cells, luminal progenitor cells, and differentiated luminal cells. This shows that when Pten is deleted, basal cells can change into intermediate cells, which is consistent with earlier studies in the area.
“Overall, our findings highlight multiple epithelial and immune cell types that are important in prostate cancer initiation and progression, as well as shed light on the interactions between specific cell populations that contribute to castration resistance,” says senior author Andrew Hsieh, Associate Professor in the Division of Human Biology, Fred Hutchinson Cancer Center, and the Department of Medicine and Genome Sciences (affiliate), University of Washington.
“We wanted to create a comprehensive, searchable database for cancer researchers while also encouraging more study in the field. As a result, we created a publicly available and interactive website that enables scientists to conduct cell- and gene-specific searches against all 50,780 cells examined in our study.”
Cells that aid in the treatment of prostate cancer resistance: A study
