The prostate is a compound tubuloalveolar exocrine gland of man's reproductive system. The main function of the prostate gland is to store and produce seminal fluid. The prostate consists of glandular epithelium embedded in a fibro-muscular stroma. The epithelium is composed of two histologically distinct layers. The secretory luminal layer is made up of tall columnar cells that are responsible for the production of PSA, PAP (prostatic acid phosphatase) and human kallikrein-2 that are secreted as part of the seminal fluid into the glandular lumina. This layer of cells is underpinned by a basal layer of cuboidal epithelial cells. The basal layer also contains a stem-like cell population that is responsible for the development of all epithelial cell types in the prostate. When the stem-like cell undergoes mitosis it gives rise to two cells, another stem cell and a daughter progenitor (transit amplifying) cell which, in turn, differentiates into a terminal end-stage secretory luminal cell.1 Within the human prostate epithelium four cell populations are discriminated by their expression of keratins. The basal cells co-localize CK5 and CK14 combined with low levels of CK18 (CK5++/14++/18+). Basal cells express low/undetectable levels of androgen receptor (AR) and are independent of androgens for their survival. The luminal cells highly express CK18 (CK18++). Luminal cells express high levels of the androgen receptor (AR) and are dependent on androgens for their survival. In addition, two intermediate subpopulations are characterized either by basal CK5++/18+- or luminal CK5+/18++- expression.2 Furthermore, it was shown that additional cell populations such as neuroendocrine cells are dispersed within the prostate epithelium. Although the function of neuroendocrine cells is largely unknown, they might induce proliferation of adjacent cells modulated by paracrine secretion of neuropeptides like chromogranin A and synaptophysin.
Epithelial homeostasis results from a steady-state equilibrium of cellular apoptosis and proliferation. The highest rate of cell death in the prostate epithelium is observed within the luminal cell layer, while apoptosis occurs at a low incidence in basal cells. Several molecular mechanisms appear to protect basal cells from apoptosis. First, senescence of basal cells is extended by telomerase activity. Furthermore, expression of the oncoprotein bcl-2 provides protection from apoptotic stimuli. Additionally, it was shown that both subgroups of basal cells, and cells with an intermediate location between the basal and luminal cell compartment, lacked expression of p27kip1. The receptors for most ligands are predominantly localized on the basal cell layer, e.g. EGFR, HER-2/neu receptor, and c-MET. Activation of these receptors can induce variable cell biological responses.3 Intermediate cells have been postulated as progenitors for prostate carcinogenesis and targets for androgen-independent tumor progression. Androgen-independency is associated with an enrichment of intermediate cells and over-expression of growth factor receptors. Targeting intermediate cells by inhibition of their growth factor receptors offers novel treatment modalities for prostate cancer. In addition, targeting the aberrant cell signaling in prostate cancer cells provides other options for patient treatment. It has been demonstrated that activation of PI3K pathway and Akt play a central role in prostate cancer initiation and progression.4 Moreover, MAP kinase, JAK/Stat, NF-KB, Notch, and other signaling pathways are also involved in proliferation and survival of prostate cancer cells.5
Human Prostate Epithelial Cells (HPrEpC) should provide a useful tool for studying various aspects of pathology and biology of the human prostate epithelium in vitro. To meet various needs for research and development, Cell Applications, Inc isolated and purified HPrEpC to create more realistic in vitro model. Cell Applications' HPrEpC are isolated from normal human prostate. They are cryopreserved at second passage and can be cultured and propagated 12 population doublings. The cells have a characteristic morphology consistent with an epithelial origin and are positive for a number of epithelial cell markers, including cytokeratin 14 and vimentin.
1. Bonkhoff, H. et al, Virchows Arch. Pathol. Anat. Histopathol. 422:35 (1993)
2. Sherwood, E.R. et al, J. Urol. 143:167 (1990)
3. Humphrey, P.A. et al, Am. J. Pathol. 147:386 (1995)
4. Dubrovska, A. et al, Proc. Natl. Acad. Sci. USA 106:268 (2009)
5. Grubb, R.L. III et al, J. Proteome Res. 8:3044 (2009)
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