Androgen receptor signalling in macrophages promotes TREM-1-mediated prostate cancer cell line migration and invasion
Menée notamment à l'aide de pièces de résection de cancer de la prostate, d'échantillons sanguins et de lignées cellulaires, cette étude met en évidence un mécanisme par lequel la signalisation du récepteur androgénique dans les macrophages favorise la migration et le processus invasif des cellules cancéreuses via le récepteur membranaire TREM-1
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.