Label retention and stem cell marker expression in the developing and adult prostate identifies basal and luminal epithelial stem cell subpopulations
(2017) In Stem Cell Research and Therapy 8(1).- Abstract
Background: Prostate cancer is the second most frequent cancer among males worldwide, and most patients with metastatic disease eventually develop therapy-resistant disease. Recent research has suggested the existence of cancer stem-like cells, and that such cells are behind the therapy resistance and progression. Methods: Here, we have taken advantage of the relatively quiescent nature of stem cells to identify the slow-cycling label-retaining stem cell (LRC) populations of the prostate gland. Mice were pulsed with bromodeoxyuridine (BrdU) during prostate organogenesis, and the LRC populations were then identified and characterized in 5-day-old and in 6-month-old adult animals using immunohistochemistry and immunofluorescence. Results:... (More)
Background: Prostate cancer is the second most frequent cancer among males worldwide, and most patients with metastatic disease eventually develop therapy-resistant disease. Recent research has suggested the existence of cancer stem-like cells, and that such cells are behind the therapy resistance and progression. Methods: Here, we have taken advantage of the relatively quiescent nature of stem cells to identify the slow-cycling label-retaining stem cell (LRC) populations of the prostate gland. Mice were pulsed with bromodeoxyuridine (BrdU) during prostate organogenesis, and the LRC populations were then identified and characterized in 5-day-old and in 6-month-old adult animals using immunohistochemistry and immunofluorescence. Results: Quantification of LRCs in the adult mouse prostate showed that epithelial LRCs were significantly more numerous in prostatic ducts (3.7 ± 0.47% SD) when compared to the proximal (1.4 ± 0.83%) and distal epithelium (0.48 ± 0.08%) of the secretory lobes. LRCs were identified in both the basal and epithelial cell layers of the prostate, and LRCs co-expressed several candidate stem cell markers in a developmental and duct/acini-specific manner, including Sca-1, TROP-2, CD133, CD44, c-kit, and the novel prostate progenitor marker cytokeratin-7. Importantly, a significant proportion of LRCs were localized in the luminal cell layer, the majority in ducts and the proximal prostate, that co-expressed high levels of androgen receptor in the adult prostate. Conclusions: Our results suggest that there are separate basal and luminal stem cell populations in the prostate, and they open up the possibility that androgen receptor-expressing luminal stem-like cells could function as cancer-initiating and relapse-responsible cells in prostate cancer.
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- author
- Ceder, Jens Adam LU ; Aalders, Tilly Wilhelmina and Schalken, Jack Antonius
- organization
- publishing date
- 2017-04-26
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Adult stem cells, Development, Label retaining, Organogenesis, Prostate
- in
- Stem Cell Research and Therapy
- volume
- 8
- issue
- 1
- article number
- 95
- publisher
- BioMed Central (BMC)
- external identifiers
-
- scopus:85018847104
- pmid:28446230
- wos:000400138200002
- ISSN
- 1757-6512
- DOI
- 10.1186/s13287-017-0544-z
- language
- English
- LU publication?
- yes
- id
- 120103e0-887d-404d-a2a5-543eec11ad38
- date added to LUP
- 2017-06-07 15:29:43
- date last changed
- 2024-04-28 13:50:04
@article{120103e0-887d-404d-a2a5-543eec11ad38,
abstract = {{<p>Background: Prostate cancer is the second most frequent cancer among males worldwide, and most patients with metastatic disease eventually develop therapy-resistant disease. Recent research has suggested the existence of cancer stem-like cells, and that such cells are behind the therapy resistance and progression. Methods: Here, we have taken advantage of the relatively quiescent nature of stem cells to identify the slow-cycling label-retaining stem cell (LRC) populations of the prostate gland. Mice were pulsed with bromodeoxyuridine (BrdU) during prostate organogenesis, and the LRC populations were then identified and characterized in 5-day-old and in 6-month-old adult animals using immunohistochemistry and immunofluorescence. Results: Quantification of LRCs in the adult mouse prostate showed that epithelial LRCs were significantly more numerous in prostatic ducts (3.7 ± 0.47% SD) when compared to the proximal (1.4 ± 0.83%) and distal epithelium (0.48 ± 0.08%) of the secretory lobes. LRCs were identified in both the basal and epithelial cell layers of the prostate, and LRCs co-expressed several candidate stem cell markers in a developmental and duct/acini-specific manner, including Sca-1, TROP-2, CD133, CD44, c-kit, and the novel prostate progenitor marker cytokeratin-7. Importantly, a significant proportion of LRCs were localized in the luminal cell layer, the majority in ducts and the proximal prostate, that co-expressed high levels of androgen receptor in the adult prostate. Conclusions: Our results suggest that there are separate basal and luminal stem cell populations in the prostate, and they open up the possibility that androgen receptor-expressing luminal stem-like cells could function as cancer-initiating and relapse-responsible cells in prostate cancer.</p>}},
author = {{Ceder, Jens Adam and Aalders, Tilly Wilhelmina and Schalken, Jack Antonius}},
issn = {{1757-6512}},
keywords = {{Adult stem cells; Development; Label retaining; Organogenesis; Prostate}},
language = {{eng}},
month = {{04}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
series = {{Stem Cell Research and Therapy}},
title = {{Label retention and stem cell marker expression in the developing and adult prostate identifies basal and luminal epithelial stem cell subpopulations}},
url = {{http://dx.doi.org/10.1186/s13287-017-0544-z}},
doi = {{10.1186/s13287-017-0544-z}},
volume = {{8}},
year = {{2017}},
}