Epithelial stem cells in human prostate growth and disease

Hudson, David L.

doi:10.1038/sj.pcan.4500745

Cited by 91 publications

(78 citation statements)

References 73 publications

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“…Human prostatic stem cells are thought to be multipotential, able to generate secretory, basal and neuroendocrine cells, located amongst basal cells that form a continuous layer between the luminal secretory cells and the basement membrane [141]. Based on colony growth in vitro, a cytokeratin-based differentiation pathway has been proposed in which stem cells are CK5/CK14-positive, giving rise to TACs that lose expression of CK14 but gain CK17 and 19 [141].…”

Section: Male Gonadal and Accessory Sex Tissuementioning

confidence: 99%

“…Based on colony growth in vitro, a cytokeratin-based differentiation pathway has been proposed in which stem cells are CK5/CK14-positive, giving rise to TACs that lose expression of CK14 but gain CK17 and 19 [141]. Richardson et al [142] found expression of CD133 in 1% of human prostate basal cells; these cells uniquely co-expressed α2β1 integrins and possessed two important attributes of putative stem cells -a high level of proliferative potential in vitro, coupled with the ability to reconstitute acini in immunocompromised mice.…”

Section: Male Gonadal and Accessory Sex Tissuementioning

confidence: 99%

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Attributes of adult stem cells

Alison

Islam

2008

The Journal of Pathology

153

115

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While cultured embryonic stem (ES) cells can be harvested in abundance and appear to be the most versatile of cells for regenerative medicine, adult stem cells also hold promise, but the identity and subsequent isolation of these comparatively rare cells remains problematic in most tissues, perhaps with the notable exception of the bone marrow. The ability to continuously self-renew and produce the differentiated progeny of the tissue of their location are their defining properties. Identifying surface molecules (markers) that would aid in stem cell isolation is a major goal. Considerable overlap exists between different putative organspecific stem cells in their repertoire of gene expression, often related to self-renewal, cell survival and cell adhesion. More robust tests of 'stemness' are now being employed, using lineage-specific genetic marking and tracking to show production of long-lived clones and multipotentiality in vivo. Moreover, the characterization of normal stem cells in specific tissues may provide a dividend for the treatment of cancer. The successful treatment of neoplastic disease may well require the specific targeting of neoplastic stem cells, cells that may well have many of the characteristics of their normal counterparts.

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Section: Male Gonadal and Accessory Sex Tissuementioning

confidence: 99%

Section: Male Gonadal and Accessory Sex Tissuementioning

confidence: 99%

Attributes of adult stem cells

Alison

Islam

2008

The Journal of Pathology

153

115

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“…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.…”

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confidence: 99%

“…[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.…”

mentioning

confidence: 99%

“…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.…”

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confidence: 99%

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

et al. 2008

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During the normal turnover of prostate epithelium, stem cells in the basal cell layer produce an intermediate cell population that gives rise to fully differentiated secretory luminal cells. This process is extensively studied in relation to the development of prostate disease, in particular, to elucidate the origin and nature of prostate cancer. We previously showed that the mRNA of a poorly characterised intercellular adhesion molecule, cadherin-10, is strongly expressed in human prostate. Using anticadherin-10 antibodies, immunohistochemistry, and confocal microscopy, we have examined the pattern of cadherin-10 expression in relation to human prostate epithelial differentiation markers (E-cadherin, CD44, and cytokeratins (CK) 14, 18 and 19) in archival paraffin-embedded and fixed-frozen histopathological specimens in individual and serial sections. In nonneoplastic prostate, E-cadherin is expressed by all basal and luminal epithelial cells, while cadherin-10 is variably expressed in luminal cells where it is colocalised with E-cadherin at basolateral plasma membranes. Cadherin-10 is absent in CK14-and/or CD44-positive basal cells, but is expressed in CK18-positive luminal cells (differentiated secretory cells), a subset of CK19-positive intermediate/luminal cells, but not CK19-positive basal cells. Small foci of prostate cancer express E-cadherin, CK19 and CK18, but cadherin-10 expression is low or undetectable. These findings suggest that the expression of cadherin-10 is associated with the later stages of differentiation of luminal secretory cells, indicating a specific role in secretory cell terminal differentiation. While prostate cancer cells express secretory cell markers (eg, CK18, prostate-specific antigen) and the more generally expressed E-cadherin, their failure to express cadherin-10 further emphasises a role for this cadherin in normal prostate organisation and function.

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Establishment and characterization of a prostate cancer cell line from a prostatectomy specimen for the study of cellular interaction

Wang

Chu

Wang

et al. 2019

Intl Journal of Cancer

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Though human prostate cancer (PCa) heterogeneity can best be studied using multiple cell types isolated from clinical specimens, the difficulty of establishing cell lines from clinical tumors has hampered this approach. In this proof‐of‐concept study, we established a human PCa cell line from a prostatectomy surgical specimen without the need for retroviral transduction. In a previous report, we characterized the stromal cells derived from PCa specimens. Here, we characterized the epithelial cells isolated from the same tumors. Compared to the ease of establishing prostate stromal cell lines, prostatic epithelial cell lines are challenging. From three matched pairs of normal and tumor tissues, we established one new PCa cell line, HPE‐15. We confirmed the origin of HPE‐15 cells by short tandem repeat microsatellite polymorphism analysis. HPE‐15 cells are androgen‐insensitive and express marginal androgen receptor, prostate‐specific antigen and prostate‐specific membrane antigen proteins. HPE‐15 expresses luminal epithelial markers of E‐cadherin and cytokeratin 18, basal cell markers of cytokeratin 5 and p63 and neuroendocrine marker of chromogranin A. Interestingly, HPE‐15 Cells exhibited no tumorigenicity in different strains of immune‐deficient mice but can become tumorigenic through interaction with aggressive cancer cell types. HPE‐15 cells can thus serve as an experimental model for the study of PCa progression, metastasis and tumor cell dormancy.

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Epithelial stem cells in human prostate growth and disease

Cited by 91 publications

References 73 publications

Attributes of adult stem cells

Attributes of adult stem cells

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

Establishment and characterization of a prostate cancer cell line from a prostatectomy specimen for the study of cellular interaction

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