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Oncotarget. 2018 Apr 10;9(27):19100-19114. doi: 10.18632/oncotarget.24913. eCollection 2018 Apr 10.

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

Author information

1
Discipline of Surgical Specialities, The University of Adelaide, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Woodville South, Australia.
2
Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
3
School of Nursing and Midwifery, Flinders University, Adelaide, Australia.
4
Molecular Oncology, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Woodville South, Australia.

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.

KEYWORDS:

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

Conflict of interest statement

CONFLICTS OF INTEREST The authors declare that they have no conflicts of interests.

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