1. Androgen receptor signalling in macrophages promotes TREM-1-mediated prostate cancer cell line migration and invasion
- Author
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Judy R. van Beijnum, Jan de Boer, Monique H.M Melis, Yoni Lubeck, Anniek Zaalberg, Mauro J. Muraro, Ingrid Hofland, Joyce Sanders, Andries M. Bergman, Erik Hooijberg, Bianca Cioni, Arjan W. Griffioen, Henk G. van der Poel, Jeroen de Jong, Wilbert Zwart, Johan van Burgsteden, Judith Vivié, Dennis Peters, CCA - Cancer biology and immunology, Medical oncology laboratory, Pathology, AII - Cancer immunology, and Chemical Biology
- Subjects
0301 basic medicine ,Male ,THP-1 Cells ,Biopsy ,General Physics and Astronomy ,SDG 3 – Goede gezondheid en welzijn ,urologic and male genital diseases ,Tosyl Compounds ,Prostate cancer ,0302 clinical medicine ,Single-cell analysis ,Robotic Surgical Procedures ,Cell Movement ,THP1 cell line ,Anilides ,Receptor ,lcsh:Science ,Multidisciplinary ,Prostate ,Middle Aged ,Neoadjuvant Therapy ,Progression-Free Survival ,Chemotherapy, Adjuvant ,Receptors, Androgen ,030220 oncology & carcinogenesis ,Cytokines ,Single-Cell Analysis ,Chemokines ,Signal Transduction ,Cancer microenvironment ,Science ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Disease-Free Survival ,Article ,03 medical and health sciences ,Stroma ,SDG 3 - Good Health and Well-being ,Cell Line, Tumor ,Nitriles ,medicine ,Humans ,Neoplasm Invasiveness ,Monocytes and macrophages ,Aged ,Prostatectomy ,Macrophages ,Prostatic Neoplasms ,Androgen Antagonists ,General Chemistry ,medicine.disease ,Coculture Techniques ,Triggering Receptor Expressed on Myeloid Cells-1 ,Androgen receptor ,030104 developmental biology ,Cell culture ,Case-Control Studies ,Blood Buffy Coat ,Cancer research ,Prostate surgery ,lcsh:Q - 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., Anti-androgen therapy inhibits prostate cancer (PC) progression, and is thought to act directly on cancer cells. Here the authors show that androgen receptor is expressed on normal and PC-associated macrophages, and its stimulation alters macrophage secretome to promote migration of cultured PC cell lines.
- Published
- 2020