Characterising the prostate stem cell niche and its architecture in benign prostatic tissue

Abstract

M. D. Thesis.Prostate cancer is the most common cancer among males in the UK with 1 in 8 men being diagnosed with the disease during their lifetimes. Despite its high prevalence and incidence, a lot about the disease process is still unknown. To understand the changes that occur in a malignant state, it is important to understand normal physiology and homeostatic mechanisms. It then becomes easier to pinpoint and understand what exactly goes wrong. Understanding the role of stem cells could also help in understanding castration-resistant prostate cancer as there could be cells that exhibit similar characteristics driving the tumour process at that point. Key among the factors in maintaining a normal physiological state is the existence of prostate stem cells and prostate stem cell niches. There was a debate about the location of these cells – and whether they were basal or luminal. Previous work done also conclusively pointed towards a basal location although there was also evidence to say that luminal stem cells existed. Further work done in the lab previously, also confirmed these findings in addition to saying that these cells were clustered at the juxta-urethral prostatic ducts. There has also been research that has pointed to the existence of stem cells by discovering two cell types that did not fit into traditional classifications of prostate cells. This study attempts to characterise the location of the stem cells and the stem cell niche within the larger context of prostate tissue. By using immunohistochemical methods to characterise each type of cell based on cell type-specific markers such as Prostate Specific Antigen and Uroplakin 1b, the aim is to paint a picture of the architecture of the stem cell niche and the surrounding microenvironment. Some positive findings from this study could only add to the evidence that there exist certain areas of the prostate tissue which do not fall under traditional categorisations of prostate epithelium or urothelium. There also exist areas of overlap between prostate and urothelium which could point towards an important overlap in their origin stories – this needs to be studied further. However, for various reasons, the methods of study need to be optimised further for better results. In conclusion, this project adds to evidence of a potential basal location for stem cells as well as talking about the various limitations with the methodologies used. In addition, there is also potential for future studies with regard to more structural as well as functional aspects of the niche including evaluating the role of stem-like cells in castration resistant prostate cancer