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; Andries M. Bergman

doi:10.1038/s41467-020-18313-y

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)

Chemical Biology

Research output: Contribution to journal › Article › Academic › peer-review

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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 language	English
Article number	4498
Number of pages	17
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-18313-y
Publication status	Published - 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.

Funders	Funder number
KWF Dutch Cancer Society
Marie Skłodowska‐Curie
KWF Kankerbestrijding

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10.1038/s41467-020-18313-y

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Cioni, B., Zaalberg, A., van Beijnum, J. R., Melis, M. H. M., van Burgsteden, J., Muraro, M. J., Hooijberg, E., Peters, D., Hofland, I., Lubeck, Y., de Jong, J., Sanders, J., Vivié, J., van der Poel, H. G., de Boer, J. P., Griffioen, A. W., Zwart, W., & Bergman, A. M. (2020). Androgen receptor signalling in macrophages promotes TREM-1-mediated prostate cancer cell line migration and invasion. Nature Communications, 11(1), Article 4498. https://doi.org/10.1038/s41467-020-18313-y

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

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.",

author = "Bianca Cioni and Anniek Zaalberg and {van Beijnum}, {Judy R.} and Melis, {Monique H.M.} and {van Burgsteden}, Johan and Muraro, {Mauro J.} and Erik Hooijberg and Dennis Peters and Ingrid Hofland and Yoni Lubeck and {de Jong}, Jeroen and Joyce Sanders and Judith Vivi{\'e} and {van der Poel}, {Henk G.} and {de Boer}, {Jan Paul} and Griffioen, {Arjan W.} and Wilbert Zwart and Bergman, {Andries M.}",

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Cioni, B, Zaalberg, A, van Beijnum, JR, Melis, MHM, van Burgsteden, J, Muraro, MJ, Hooijberg, E, Peters, D, Hofland, I, Lubeck, Y, de Jong, J, Sanders, J, Vivié, J, van der Poel, HG, de Boer, JP, Griffioen, AW, Zwart, W & Bergman, AM 2020, 'Androgen receptor signalling in macrophages promotes TREM-1-mediated prostate cancer cell line migration and invasion', Nature Communications, vol. 11, no. 1, 4498. https://doi.org/10.1038/s41467-020-18313-y

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T1 - Androgen receptor signalling in macrophages promotes TREM-1-mediated prostate cancer cell line migration and invasion

AU - Cioni, Bianca

AU - Zaalberg, Anniek

AU - van Beijnum, Judy R.

AU - Melis, Monique H.M.

AU - van Burgsteden, Johan

AU - Muraro, Mauro J.

AU - Hooijberg, Erik

AU - Peters, Dennis

AU - Hofland, Ingrid

AU - Lubeck, Yoni

AU - de Jong, Jeroen

AU - Sanders, Joyce

AU - Vivié, Judith

AU - van der Poel, Henk G.

AU - de Boer, Jan Paul

AU - Griffioen, Arjan W.

AU - Zwart, Wilbert

AU - Bergman, Andries M.

PY - 2020/12/1

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N2 - 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.

AB - 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.

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

Abstract

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UN SDGs

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