Principles of stem cell biology and cancer: future applications and therapeutics. Edited by T. Regad, T. J. Sayers and R. C. Rees. John Wiley & Sons (2015)
The prostate is a male sex accessory organ located directly beneath the bladder and adjacent to the anus (Timms, 2008). The normal function of the prostate is to produce and excrete seminal secretions, which provide a lubricant and a fluid medium for spermatozoa (Thomson and Marker, 2006). The prostate develops from the urogenital sinus (UGS) structure, comprising a mesodermally derived mesenchymal layer surrounding an endodermally derived epithelial layer. The initiation of prostatic morphogenesis is mediated by the outgrowth of solid epithelial buds from the epithelial – urogenital sinus (E-UGS) into the mesenchymal – urogenital sinus (M-UGS) (Timms et al., 1994). The initial development of prostate growth results from induction of paracrine signalling between the two types of layers by mesenchymal and epithelial interactions, a phenomenon also seen in the development of the lungs, the kidneys and the gut (Cunha et al., 2004). The prostatic buds form solid cords of epithelial cells that grow into the M-USG in a spatial pattern, initiating the process of branching. Epithelial and mesenchymal/stromal interactions have been shown to be responsible for this cytodifferentiation (Wang et al., 2001). Following ductal canalization, the epithelium reorganizes into four final differentiated prostate cell types: basal, luminal, neuroendocrine (NE) and transit-amplifying cells (TACs), which are defined by their distinct morphology, their locations and their markers’ expression patterns (Prajapati et al., 2013).
The luminal region comprises the majority of the prostate cells, forming a layer of baso-apical cells that secrete prostatic proteins such as prostaticspecific antigen (PSA), prostatic acid phosphatase (PAP) and fluids into the ductal lumen. These cells are terminally differentiated, androgen-dependent and characterized by the expression of cytokeratins 8 and 18, CD57 and p27 (a cell-cycle inhibitor), along with high levels of androgen receptors (ARs) (De Marzo et al., 1998; Wang et al., 2001; Long et al., 2005). The basal epithelial cells form a layer of flattened cuboidal cells along the basement membrane and express cytokeratins 5 and 14, as well as p63 (a homologue of the tumour-suppressor gene p53), Bcl-2 (an antiapoptotic factor), CD44 and the hepatocyte growth factor (HGF). Basal cells exist independent of androgen signalling and express undetectable levels of ARs (Bonkhoff and Remberger, 1993; Wang et al., 2001; Long et al., 2005). NE cells are a rare cell population found along the basal and luminal cell layers, characterized by their androgen independence and the expression of chromogranin A, synaptophysin and neurotensin (Abrahamsson, 1999; Abate-Shen and Shen, 2000; Amorino and Parsons, 2004). TACs, an intermediate cell population, express both basal and luminal cell markers (CK5, CK8, CK14, ARs and PSA) (Bonkhoff and Remberger, 1993; Bonkhoff et al., 1994; Xue et al., 1998; Abrahamsson, 1999; Hudson et al., 2000). Finally, the prostate ductal structure is surrounded by a stromal layer, which acts as a peripheral boundary to the prostate gland. The stromal compartment is built from several types of cells, including smooth-muscle cells, fibroblasts and myofibroblasts, and is characterized by the expression of CD34, CD44, CD90, CD117 and vimentin (Takao and Tsujimura, 2008).