Identification, properties, and clinical significance of putative stem-like cell populations in prostate cancer

The notion that tumour initiation and heterogeneity might be driven by small population of tumour-initiating cells (TIC) has gained high significance since the pioneering identification of TIC in leukaemia. This has led to a worldwide research effort to further identify TIC in solid tumours.
In prostate cancer (PCa), however, demonstration of the existence and identification of TIC have been hampered by a lack of consistent in vitro and in vivo models. Chapter I of this thesis presents several models of human PCa and their respective significance to study TIC in PCa. This chapter also describes my attempts to establish more relevant models by generating and characterising short-term primary cultures derived from clinical PCa specimens.
TIC are thought to share some properties of normal stem cells and to express genes typically expressed by embryonic stem cells. Based on this hypothesis, I investigated the expression of stemness-associated genes in PCa. Findings are presented in Chapter II of the thesis and described in the published manuscript entitled “Klf4 transcription factor is expressed in the cytoplasm of prostate cancer cells”.
Additionally, same as normal stem cells, TIC might display high activity of aldehyde dehydrogenase (ALDH) enzyme. Chapter III reports the characterisation of a cell subset exhibiting high ALDH activity in PCa. In particular, features, prevalence and clinical significance of these cells in PCa are presented in the manuscript entitled “Characterization and clinical relevance of ALDHbright populations in prostate cancer”.
Taken together, my thesis highlights the complexity of the TIC concept and the urgent need for more accurate models, paving the way for further studies aiming at identifying TIC in human PCa.