Androgen Receptor Signalling in Macrophages Promotes TREM-1 mediated Cell Migration and Invasion pluripotent and lineage-committed cells.

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 play a decisive role in PCa initiation and progression, however, the role of AR in these cells remains largely unexplored. Here we show that AR signalling in macrophage-like THP-1 cell line supports PCa cell line migration and invasion in culture via increased Triggering REceptor of Macrophage-1 (TREM-1) signalling and expression of its downstream cytokines. THP-1 cells were stimulated with 20ng/ml of PMA in hormone-deprived medium for 2 days, followed by stimulation with 10ng/ml of LPS and 10ng/ml of IFNɣ for 24 hrs. Cells were then stimulated for 4 hours with 10nM of R1881 (synthetic testosterone) or DMSO control. Then, cells were fixed for 10 minutes with 1% formaldehyde, quenched with glycine and lysed in LB1, LB2 and LB3 (Schmidt et al, 2009). Lysates were incubated with antibodies for AR or H3K27ac.