Delta-Like 1 (Dlk-1), a Novel Marker of Prostate Basal and Candidate Epithelial Stem Cells, Is Downregulated by Notch Signalling in Intermediate/Transit Amplifying Cells of the Human Prostate.
(2008) In European Urology 54. p.1344-1353- Abstract
- BACKGROUND: There is a lack of understanding of the processes that regulate differentiation in the prostate. OBJECTIVE: To determine localisation, activity, and regulation of cytodifferentiation-modulatory proteins in the human adult prostate. DESIGN, SETTINGS, AND PARTICIPANTS: Eighteen volunteering patients with organ-confined prostate cancer were prospectively enrolled at a single university hospital. INTERVENTION: All patients underwent radical prostatectomy, and normal/benign tissue was excised and obtained from the transition zone. MEASUREMENTS: Expression and activity of Notch-protein family members, including the Notch-homologous protein Delta-like 1 (Dlk-1/Pref1), were investigated immunohistochemically in normal/benign tissue and... (More)
- BACKGROUND: There is a lack of understanding of the processes that regulate differentiation in the prostate. OBJECTIVE: To determine localisation, activity, and regulation of cytodifferentiation-modulatory proteins in the human adult prostate. DESIGN, SETTINGS, AND PARTICIPANTS: Eighteen volunteering patients with organ-confined prostate cancer were prospectively enrolled at a single university hospital. INTERVENTION: All patients underwent radical prostatectomy, and normal/benign tissue was excised and obtained from the transition zone. MEASUREMENTS: Expression and activity of Notch-protein family members, including the Notch-homologous protein Delta-like 1 (Dlk-1/Pref1), were investigated immunohistochemically in normal/benign tissue and explant cultures. The effect of the Notch inhibitor L-685,458 on Dlk-1 expression and cell number was investigated in primary cell cultures, and data were analysed with Student t test. RESULTS AND LIMITATIONS: Mature luminal cells were found to co-express Notch-1 and its ligand Jagged1, but epithelia in normal/benign tissue showed no active Notch signalling. The basal cell layer, rare candidate epithelial stem cells, and a subpopulation of neuroendocrine cells expressed the differentiation protein Dlk-1. In explant cultures, luminal cells and Jagged1 expression were lost, whereas intermediate cells downregulated Dlk-1 concomitant with Notch-1 upregulation and activation. Notch inhibition in primary cell cultures led to lower cell densities (p<0.001) and suppressed downregulation of Dlk-1. This is a small study; current results need to be confirmed in larger investigations. CONCLUSIONS: We demonstrate that Notch-1 is upregulated in differentiation of prostate epithelia, and that the novel prostate progenitor marker Dlk-1 is downregulated by Notch signalling in intermediate cells. The identification of Dlk-1-expressing candidate stem and neuroendocrine cells suggests a hierarchical relationship. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1147960
- author
- Ceder, Jens LU ; Jansson, Linda LU ; Helczynski, Leszek LU and Abrahamsson, Per-Anders LU
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- in
- European Urology
- volume
- 54
- pages
- 1344 - 1353
- publisher
- Elsevier
- external identifiers
-
- wos:000261677600018
- pmid:18375047
- scopus:55449114581
- ISSN
- 1873-7560
- DOI
- 10.1016/j.eururo.2008.03.006
- language
- English
- LU publication?
- yes
- id
- 386a2f1c-a4ed-4fb6-b812-39b69438d4ca (old id 1147960)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/18375047?dopt=Abstract
- date added to LUP
- 2016-04-04 09:11:34
- date last changed
- 2022-01-29 08:44:31
@article{386a2f1c-a4ed-4fb6-b812-39b69438d4ca,
abstract = {{BACKGROUND: There is a lack of understanding of the processes that regulate differentiation in the prostate. OBJECTIVE: To determine localisation, activity, and regulation of cytodifferentiation-modulatory proteins in the human adult prostate. DESIGN, SETTINGS, AND PARTICIPANTS: Eighteen volunteering patients with organ-confined prostate cancer were prospectively enrolled at a single university hospital. INTERVENTION: All patients underwent radical prostatectomy, and normal/benign tissue was excised and obtained from the transition zone. MEASUREMENTS: Expression and activity of Notch-protein family members, including the Notch-homologous protein Delta-like 1 (Dlk-1/Pref1), were investigated immunohistochemically in normal/benign tissue and explant cultures. The effect of the Notch inhibitor L-685,458 on Dlk-1 expression and cell number was investigated in primary cell cultures, and data were analysed with Student t test. RESULTS AND LIMITATIONS: Mature luminal cells were found to co-express Notch-1 and its ligand Jagged1, but epithelia in normal/benign tissue showed no active Notch signalling. The basal cell layer, rare candidate epithelial stem cells, and a subpopulation of neuroendocrine cells expressed the differentiation protein Dlk-1. In explant cultures, luminal cells and Jagged1 expression were lost, whereas intermediate cells downregulated Dlk-1 concomitant with Notch-1 upregulation and activation. Notch inhibition in primary cell cultures led to lower cell densities (p<0.001) and suppressed downregulation of Dlk-1. This is a small study; current results need to be confirmed in larger investigations. CONCLUSIONS: We demonstrate that Notch-1 is upregulated in differentiation of prostate epithelia, and that the novel prostate progenitor marker Dlk-1 is downregulated by Notch signalling in intermediate cells. The identification of Dlk-1-expressing candidate stem and neuroendocrine cells suggests a hierarchical relationship.}},
author = {{Ceder, Jens and Jansson, Linda and Helczynski, Leszek and Abrahamsson, Per-Anders}},
issn = {{1873-7560}},
language = {{eng}},
pages = {{1344--1353}},
publisher = {{Elsevier}},
series = {{European Urology}},
title = {{Delta-Like 1 (Dlk-1), a Novel Marker of Prostate Basal and Candidate Epithelial Stem Cells, Is Downregulated by Notch Signalling in Intermediate/Transit Amplifying Cells of the Human Prostate.}},
url = {{http://dx.doi.org/10.1016/j.eururo.2008.03.006}},
doi = {{10.1016/j.eururo.2008.03.006}},
volume = {{54}},
year = {{2008}},
}