Stem/progenitor and intermediate cell types and the origin of human prostate cancer

Tokar, Erik J.; Ancrile, Brooke B.; Cunha, Gerald R.; Webber, Mukta M.

doi:10.1111/j.1432-0436.2005.00047.x

Cited by 93 publications

(94 citation statements)

References 50 publications

(94 reference statements)

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“…Our observation that PROMININ-2 is predominantly expressed in the basal cells of the human prostatic epithelium is in line with the diVerential gene expression observed between cells morphologically segregated into basal and luminal compartments (Terpe et al 1994;Signoretti et al 2000;Tokar et al 2005). Although not free from controversies, several observations indicate that basal and secretory cells are hierarchically related, where basal cells represent (or include) the progenitors for terminally diVerentiated luminal ones implying that the adult stem cells responsible for homeostatic replacement reside in the basal compartment (Aumüller 1991;BonkhoV and Remberger, 1996;Robinson et al 1998;Signoretti et al 2005;Signoretti and Loda 2006).…”

Section: Discussionsupporting

confidence: 85%

“…Inasmuch as these prostate cancer cells predominantly display more luminal, secretory-like phenotypes this might indicate that the diVerentiation grade of the prostate tumors could negatively correlate with PROMININ-2 expression. Whether PROMININ-2 might be a marker of both normal and/or tumor initiating progenitor cells or is expressed by the putative intermediate "transit ampliWer" pool of cells with mixed immunophenotypic proWle (van Leenders et al 2000;Tran et al 2002;Schalken and van Leenders 2003;Tokar et al 2005) remains to be established. Likewise, the potential expression of PROMININ-2 by neuroendocrine cells being sparsely scattered between the basal and luminal layers (Noordzij et al 1995) needs to be investigated as well.…”

Section: Discussionmentioning

confidence: 99%

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Robust expression of Prominin-2 all along the adult male reproductive system and urinary bladder

Jászai

Fargeas

Haase

et al. 2008

Histochem Cell Biol

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Although the male reproductive system seems to be enriched in transcripts encoding for both Prominin genes, little is known about their spatial distribution in distinct segments of this organ system. This is especially true for the less-characterized second Prominin paralogue, Prominin-2. The present study, therefore, mainly examines the expression of Prominin-2 in male mice and reveals the existence of some crucial diVerences in the tissue compartmentalization of the two Prominin paralogues in the testis, epididymis, seminal vesicle, prostate and urinary bladder. Our in situ hybridization analysis demonstrates that the major domains of overlapping expression between the two Prominin genes are those compartments that are derived ontogenetically from the epigonadal mesonephric tubules, i.e. ductuli eVerentes, or from the WolYan-tube/ductus mesonephricus, for instance the corpus epididymidis and vesicula seminalis. In contrast, the sinus urogenitalis derivative urinary bladder epithelium expresses exclusively Prominin-2, but not Prominin-1 (CD133). The testis expresses only Prominin-1, not Prominin-2. In human prostate, we Wnally demonstrate that the expression of Prominin-2 (transcript and protein) is highly enriched in cells located in the basal compartment of the glandular epithelium where only a minute population was recently reported to be Prominin-1 positive. Taken together our data indicate that, except for the gonad, Prominin-2 is widely and abundantly expressed along the epithelia of various segments of the adult male genitourinary tract.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Robust expression of Prominin-2 all along the adult male reproductive system and urinary bladder

Jászai

Fargeas

Haase

et al. 2008

Histochem Cell Biol

View full text Add to dashboard Cite

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“…Accumulating evidence suggests that the bulk of prostate cancer arises from self-renewing cancer stem cells whose progeny undergo differentiation to cancer cells of low proliferative and tumour-forming capacity. [29][30][31][32] The origin of these cells (ie, the cellular target of malignant transformation) is not clear, though the predominance of the intermediate/secretory phenotypes in cancer suggest an early intermediate cell target. E-cadherin þ / CK19 þ /CK18 þ cancer cells lack cadherin-10.…”

Section: Discussionmentioning

confidence: 99%

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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“…TRAMP mice were mated with the floxed AR transgenic mice to obtain TRAMP mice carrying the floxed AR transgene, which in turn were crossed with probasin-Cre mice to generate prostate epithelial-specific (pes)-ARKO-TRAMP mice (Niu et al, 2008a, b). Prostatic epithelial cells develop from stem cells through proliferation and differentiation into basal and intermediate cells that finally differentiate into epithelial luminal cells (Litvinov et al, 2003;Tokar et al, 2005). AR is expressed in about 50% of the basal cells and all of the luminal cells in mouse prostate (Mirosevich et al, 1999;Niu et al, 2008a).…”

Section: Ar Dual Functions In Prostate Cancer Progression and Metastasismentioning

confidence: 99%

Differential androgen receptor signals in different cells explain why androgen-deprivation therapy of prostate cancer fails

et al. 2010

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Prostate cancer is one of the major causes of cancerrelated death in the western world. Androgen-deprivation therapy (ADT) for the suppression of androgens binding to the androgen receptor (AR) has been the norm of prostate cancer treatment. Despite early success to suppress prostate tumor growth, ADT eventually fails leading to recurrent tumor growth in a hormonerefractory manner, even though AR remains to function in hormone-refractory prostate cancer. Interestingly, some prostate cancer survivors who received androgen replacement therapy had improved quality of life without adverse effect on their cancer progression. These contrasting clinical data suggest that differential androgen/ AR signals in individual cells of prostate tumors can exist in the same or different patients, and may be used to explain why ADT of prostate cancer fails. Such a hypothesis is supported by the results obtained from transgenic mice with selective knockout of AR in prostatic stromal vs epithelial cells and orthotopic transplants of various human prostate cancer cell lines with AR overexpression or knockout. These studies concluded that AR functions as a stimulator for prostate cancer proliferation and metastasis in stromal cells, as a survival factor of prostatic cancer epithelial luminal cells, and as a suppressor for prostate cancer basal intermediate cell growth and metastasis. These dual yet opposite functions of the stromal and epithelial AR may challenge the current ADT to battle prostate cancer and should be taken into consideration when developing new AR-targeting therapies in selective prostate cancer cells.

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Stem/progenitor and intermediate cell types and the origin of human prostate cancer

Cited by 93 publications

References 50 publications

Robust expression of Prominin-2 all along the adult male reproductive system and urinary bladder

Robust expression of Prominin-2 all along the adult male reproductive system and urinary bladder

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

Differential androgen receptor signals in different cells explain why androgen-deprivation therapy of prostate cancer fails

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