Myofibroblast androgen receptor expression determines cell survival in co-cultures of myofibroblasts and prostate cancer cells in vitro.
Author(s)
Palethorpe, Helen M
Leach, Damien A
Need, Eleanor F
Drew, Paul A
Smith, Eric
Type
Journal Article
Abstract
Fibroblasts express androgen receptor (AR) in the normal prostate and during prostate cancer development. We have reported that loss of AR expression in prostate cancer-associated fibroblasts is a poor prognostic indicator. Here we report outcomes of direct and indirect co-cultures of immortalised AR-positive (PShTert-AR) or AR-negative (PShTert) myofibroblasts with prostate cancer cells. In the initial co-cultures the AR-negative PC3 cell line was used so AR expression and signalling were restricted to the myofibroblasts. In both direct and indirect co-culture with PShTert-AR myofibroblasts, paracrine signalling to the PC3 cells slowed proliferation and induced apoptosis. In contrast, PC3 cells proliferated with PShTert myofibroblasts irrespective of the co-culture method. In direct co-culture PC3 cells induced apoptosis in and destroyed PShTerts by direct signalling. Similar results were seen in direct co-cultures with AR-negative DU145 and AR-positive LNCaP and C4-2B prostate cancer cell lines. The AR ligand 5α-dihydrotestosterone (DHT) inhibited the proliferation of the PShTert-AR myofibroblasts, thereby reducing the extent of their inhibitory effect on cancer cell growth. These results suggest loss of stromal AR would favour prostate cancer cell growth in vivo, providing an explanation for the clinical observation that reduced stromal AR is associated with a poorer outcome.
Date Issued
2018-04-10
Date Acceptance
2018-03-06
Citation
Oncotarget, 2018, 9 (27), pp.19100-19114
ISSN
1949-2553
Publisher
Impact Journals
Start Page
19100
End Page
19114
Journal / Book Title
Oncotarget
Volume
9
Issue
27
Copyright Statement
Copyright: Palethorpe et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License
3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and
source are credited.
3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and
source are credited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/29721186
PII: 24913
Subjects
androgen receptor
direct co-culture
indirect co-culture
myofibroblast
prostate cancer
Publication Status
Published online
Coverage Spatial
United States