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Label retention and stem cell marker expression in the developing and adult prostate identifies basal and luminal epithelial stem cell subpopulations

Ceder, Jens Adam LU ; Aalders, Tilly Wilhelmina and Schalken, Jack Antonius (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
organization
publishing date
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
publisher
BioMed Central
external identifiers
  • scopus:85018847104
  • 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
2018-01-07 12:06:23
@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>},
  articleno    = {95},
  author       = {Ceder, Jens Adam and Aalders, Tilly Wilhelmina and Schalken, Jack Antonius},
  issn         = {1757-6512},
  keyword      = {Adult stem cells,Development,Label retaining,Organogenesis,Prostate},
  language     = {eng},
  month        = {04},
  number       = {1},
  publisher    = {BioMed Central},
  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},
  volume       = {8},
  year         = {2017},
}