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

Bianca Cioni, Anniek Zaalberg, Judy R. van Beijnum, Monique H.M. Melis, Johan van Burgsteden, Mauro J. Muraro, Erik Hooijberg, Dennis Peters, Ingrid Hofland, Yoni Lubeck, Jeroen de Jong, Joyce Sanders, Judith Vivié, Henk G. van der Poel, Jan Paul de Boer, Arjan W. Griffioen, Wilbert Zwart (Corresponding author), Andries M. Bergman (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

64 Citations (Scopus)

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.

Original languageEnglish
Article number4498
Number of pages17
JournalNature Communications
Volume11
Issue number1
DOIs
Publication statusPublished - 1 Dec 2020

Funding

The authors thank the Genomics core facility and Core Facility Molecular Pathology and Biobanking of NKI and the Sorting facility of the Hubrecht Institute for their technical support. The authors kindly thank Dr. Yongsoo Kim for bioinformatics support. This work was supported by grants from Marie Curie ITN-TIMCC and KWF Dutch Cancer Society.

FundersFunder number
KWF Dutch Cancer Society
Marie Skłodowska‐Curie
KWF Kankerbestrijding

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