Oncotarget

Research Papers:

Myofibroblast androgen receptor expression determines cell survival in co-cultures of myofibroblasts and prostate cancer cells in vitro

Helen M. Palethorpe, Damien A. Leach, Eleanor F. Need, Paul A. Drew _ and Eric Smith

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2018; 9:19100-19114. https://doi.org/10.18632/oncotarget.24913

Metrics: PDF 1183 views  |   HTML 1190 views  |   ?  


Abstract

Helen M. Palethorpe1, Damien A. Leach1,2, Eleanor F. Need1, Paul A. Drew1,3,* and Eric Smith1,4,*

1Discipline of Surgical Specialities, The University of Adelaide, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Woodville South, Australia

2Department of Surgery and Cancer, Imperial College London, London, United Kingdom

3School of Nursing and Midwifery, Flinders University, Adelaide, Australia

4Molecular Oncology, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Woodville South, Australia

*These authors are contributed equally to this work

Correspondence to:

Paul A. Drew, email: paul.drew@flinders.edu.au

Keywords: androgen receptor; direct co-culture; indirect co-culture; myofibroblast; prostate cancer

Received: February 28, 2018     Accepted: March 06, 2018     Published: April 10, 2018

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 24913