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PROSTATE CANCER STEM CELLS
easily discernible. A concept of anatomical zones which considers the site of origin of different pathologies is used instead.[2] The prostate is then described in terms of a peripheral, a central, and a transition zone as well as an anterior fibromuscular stroma. Benign prostate hyperplasia (BPH) originates mainly in the transition zone, whereas prostate carcinomas commonly arise in the peripheral zone of the prostate.[3] Histologically, the prostate exhibits a tuboloalveolar gland architecture. An epithelial parenchyma is embedded within a connective tissue matrix, and epithelial cells are organized in glands that branch out from the urethra and terminate in secretory acini (Fig. 7.1). In adults, the prostate epithelium is organized as a bilayer consisting of a basal layer of flattened, undifferentiated cells attached to the basement membrane and a layer of terminally differentiated, columnar secretory cells residing on top of the basal cells and facing the gland lumen. This characteristic two-layered epithelial architecture develops during puberty under the influence of male sex hormones. Prior to this differentiation process, prostatic ducts and acini are lined with a multilayered epithelium consisting of immature cells.[4] A third cell type discernible in adult prostate comprises the neuroendocrine cells, which are scattered throughout the basal compartment. They are characterized by the expression of neuropeptides such as chromogranin and serotonin, and are terminally differentiated androgen-insensitive cells.[5] Luminal cells are characterized by expression of the differentiation markers androgen receptor (AR), prostatic acid phosphatase (PAP), and prostate-specific antigen (PSA), which is currently used as a diagnostic marker for early prostate cancer.[6] Basal cells, in contrast, express the antiapoptotic gene bcl-2.[7;8] Both basal and luminal cells also express a characteristic set of cytokeratins, which commonly serve as specific
secretory cells secretory duct
basal cell ductal lumen prostatic fluid
FIGURE 7.1 Organization of the prostate gland: cross section of the ductal region with labels indicating cell types present in prostatic ducts, including luminal secretory and basal cells. (From A.T. Collins and N.J. Maitland, Prostate cancer stem cells, Eur. J. Cancer, 2006; 42:1213–1218.)