Prostate epithelial cell differentiation and its relevance to the understanding of prostate cancer therapies

Abstract

Prostate cancer is the most common malignancy in males in the western world. However, little is known about its origin and development. This review highlights the biology of the normal prostate gland and the differentiation of basal epithelial cells to a secretory phenotype. Alterations in this differentiation process leading to cancer and androgen-independent disease are discussed, as well as a full characterization of prostate epithelial cells. A full understanding of the origin and characteristics of prostate cancer epithelial cells will be important if we are to develop therapeutic strategies to combat the heterogeneous nature of this disease.

The intercellular adhesion molecule, cadherin-10, is a marker for human prostate luminal epithelial cells that is not expressed in prostate cancer

“…3,7,[26][27][28] In some glandular profiles, CK19 was strongly expressed in basal cells, but weak or absent in luminal cells, while in other glands, cells in luminal positions strongly expressed CK19 (Figure 4). CK19-positive cells can appear to be intercalated between CK19-negative luminal cells in some glands (Figure 4 Cadherin-10 and the Luminal Cell Marker, CK18, in Normal Human Prostate Epithelium CK18 is well-established as a marker for luminal secretory cells, 3,5,6,27 and the staining pattern we observed was consistent with this ( Figure 5). CK18 is present in luminal cells, but is not observed in …”

“…1 The basal cell layer is believed to contain a subpopulation of stem cells that produce transit amplifying cells whose progeny undergo a programme of differentiation, via intermediate cells, towards fully differentiated luminal secretory cells. [2][3][4][5][6][7] In human prostate tissue samples, the glandular epithelium typically exhibits phenotypic heterogeneity reflecting stages of differentiation during turnover and repair. 5 Understanding this differentiation process is crucial to a more complete understanding of the origin and development of prostate disease, in particular, prostate cancer.…”

“…[2][3][4][5][6] This was initially interpreted as suggesting that they arose from transformed luminal epithelium, however, it is now known that both androgen-dependent and androgen-independent prostate cancer cells also express basal and intermediate cell characteristics that are normally lost by differentiating luminal cells (eg, CK19). Such evidence indicates that prostate cancer arises from malignant transformation of intermediate cells, and that the expression of luminal cell markers in these cancer cells is due to the aberrant differentiation of transformed intermediate cells.…”

“…Such evidence indicates that prostate cancer arises from malignant transformation of intermediate cells, and that the expression of luminal cell markers in these cancer cells is due to the aberrant differentiation of transformed intermediate cells. [2][3][4][5][6] Intercellular adhesion is a key factor in epithelial tissue morphogenesis and maintenance, and perturbation of this adhesion is of considerable importance in cancer. Cadherins are a family of Ca 2 þ -dependent cell-cell adhesion molecules with well-established roles in cell-cell recognition, intercellular junction organisation and cell differentiation.…”

Chemo-hormone therapy of non-well-differentiated endocrine tumours from different anatomic sites with cisplatinum, etoposide and slow release lanreotide formulation

“…In this case, the derivative cells may dynamically undergo a caricatural differentiation that may resemble epithelial, glandular, or neuroendocrine cells. On the basis of different kinds and levels of molecular and genetic alterations, these cells may follow distinct differentiation pathways and may stop their distinct differentiation programmes at different stages of maturation (Buchanan et al, 1986;Hansson and Abrahamsson, 2003;Wright et al, 2003;Bishop, 2005;Long et al, 2005). Respiratory, gastroenteric, and urinary tracts, as well as the prostate, are physiologically under strict neurovegetative control, and so it is not surprising that the majority of neuroendocrine tumours arise in these anatomic sites.…”