Androgen receptor signalling in macrophages promotes TREM-1-mediated prostate cancer cell line migration and invasion

Bianca Cioni, Anniek Zaalberg, Judy R. Beijnum, Monique H. M. Melis, Johan Burgsteden, Mauro J. Muraro, Erik Hooijberg, Dennis Peters, Ingrid Hofland, Yoni Lubeck, Jeroen Jong, Joyce Sanders, Judith Vivié, Henk G. Poel, Jan Paul Boer, Arjan W. Griffioen, Wilbert Zwart () and Andries M. Bergman ()
Additional contact information
Bianca Cioni: Divisions of Oncogenomics, The Netherlands Cancer Institute (NKI)
Anniek Zaalberg: Divisions of Oncogenomics, The Netherlands Cancer Institute (NKI)
Judy R. Beijnum: Angiogenesis laboratory, Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam
Monique H. M. Melis: Molecular Genetics, NKI
Johan Burgsteden: Molecular Genetics, NKI
Mauro J. Muraro: Hubrecht Institute - KNAW and University Medical Center Utrecht
Erik Hooijberg: Division of Pathology, NKI
Dennis Peters: Core Facility Molecular Pathology, NKI
Ingrid Hofland: Core Facility Molecular Pathology, NKI
Yoni Lubeck: Division of Pathology, NKI
Jeroen Jong: Division of Pathology, NKI
Joyce Sanders: Division of Pathology, NKI
Judith Vivié: Hubrecht Institute - KNAW and University Medical Center Utrecht
Henk G. Poel: Urology and Medical Oncology, NKI
Jan Paul Boer: Urology and Medical Oncology, NKI
Arjan W. Griffioen: Angiogenesis laboratory, Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam
Wilbert Zwart: Divisions of Oncogenomics, The Netherlands Cancer Institute (NKI)
Andries M. Bergman: Divisions of Oncogenomics, The Netherlands Cancer Institute (NKI)

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: Abstract The androgen receptor (AR) is the master regulator of prostate cancer (PCa) development, and inhibition of AR signalling is the most effective PCa treatment. AR is expressed in PCa cells and also in the PCa-associated stroma, including infiltrating macrophages. Macrophages have a decisive function in PCa initiation and progression, but the role of AR in macrophages remains largely unexplored. Here, we show that AR signalling in the macrophage-like THP-1 cell line supports PCa cell line migration and invasion in culture via increased Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) signalling and expression of its downstream cytokines. Moreover, AR signalling in THP-1 and monocyte-derived macrophages upregulates IL-10 and markers of tissue residency. In conclusion, our data suggest that AR signalling in macrophages may support PCa invasiveness, and blocking this process may constitute one mechanism of anti-androgen therapy.

Date: 2020
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DOI: 10.1038/s41467-020-18313-y

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