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^*, Andries M. Bergman

^*Corresponding author for this work

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

1 Downloads (Pure)

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

Keywords

Aged
Androgen Antagonists/pharmacology
Anilides/pharmacology
Biopsy
Blood Buffy Coat/cytology
Case-Control Studies
Cell Line, Tumor
Cell Movement/drug effects
Chemotherapy, Adjuvant
Coculture Techniques
Disease-Free Survival
Humans
Macrophages/immunology
Male
Middle Aged
Neoadjuvant Therapy
Neoplasm Invasiveness/immunology
Nitriles/pharmacology
Progression-Free Survival
Prostate/pathology
Prostatectomy
Prostatic Neoplasms/immunology
Receptors, Androgen/metabolism
Robotic Surgical Procedures
Signal Transduction/immunology
Single-Cell Analysis
THP-1 Cells
Tosyl Compounds/pharmacology
Triggering Receptor Expressed on Myeloid Cells-1/metabolism

Access to Document

10.1038/s41467-020-18313-y

s41467-020-18313-yFinal published version, 4 MB

Cite this

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

@article{8be53f575e1f4458a457a2f6bec6cb36,

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.",

keywords = "Aged, Androgen Antagonists/pharmacology, Anilides/pharmacology, Biopsy, Blood Buffy Coat/cytology, Case-Control Studies, Cell Line, Tumor, Cell Movement/drug effects, Chemotherapy, Adjuvant, Coculture Techniques, Disease-Free Survival, Humans, Macrophages/immunology, Male, Middle Aged, Neoadjuvant Therapy, Neoplasm Invasiveness/immunology, Nitriles/pharmacology, Progression-Free Survival, Prostate/pathology, Prostatectomy, Prostatic Neoplasms/immunology, Receptors, Androgen/metabolism, Robotic Surgical Procedures, Signal Transduction/immunology, Single-Cell Analysis, THP-1 Cells, Tosyl Compounds/pharmacology, Triggering Receptor Expressed on Myeloid Cells-1/metabolism",

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.}",

year = "2020",

month = dec,

day = "1",

doi = "10.1038/s41467-020-18313-y",

language = "English",

volume = "11",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

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

TY - JOUR

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

Y1 - 2020/12/1

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.

KW - Aged

KW - Androgen Antagonists/pharmacology

KW - Anilides/pharmacology

KW - Biopsy

KW - Blood Buffy Coat/cytology

KW - Case-Control Studies

KW - Cell Line, Tumor

KW - Cell Movement/drug effects

KW - Chemotherapy, Adjuvant

KW - Coculture Techniques

KW - Disease-Free Survival

KW - Humans

KW - Macrophages/immunology

KW - Male

KW - Middle Aged

KW - Neoadjuvant Therapy

KW - Neoplasm Invasiveness/immunology

KW - Nitriles/pharmacology

KW - Progression-Free Survival

KW - Prostate/pathology

KW - Prostatectomy

KW - Prostatic Neoplasms/immunology

KW - Receptors, Androgen/metabolism

KW - Robotic Surgical Procedures

KW - Signal Transduction/immunology

KW - Single-Cell Analysis

KW - THP-1 Cells

KW - Tosyl Compounds/pharmacology

KW - Triggering Receptor Expressed on Myeloid Cells-1/metabolism

UR - http://www.scopus.com/inward/record.url?scp=85090398759&partnerID=8YFLogxK

U2 - 10.1038/s41467-020-18313-y

DO - 10.1038/s41467-020-18313-y

M3 - Article

C2 - 32908142

AN - SCOPUS:85090398759

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 4498

ER -

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this