雄激素受体信号在巨噬细胞中促进 TREM-1 介导体前列腺癌细胞系的迁移和侵袭。

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

机构信息

Divisions of Oncogenomics, The Netherlands Cancer Institute (NKI), Plesmanlaan 121, 1066CX, Amsterdam, The Netherlands.

Angiogenesis laboratory, Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.

出版信息

Nat Commun. 2020 Sep 9;11(1):4498. doi: 10.1038/s41467-020-18313-y.

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.

雄激素受体（AR）是前列腺癌（PCa）发展的主要调节因子，抑制 AR 信号通路是最有效的 PCa 治疗方法。AR 在 PCa 细胞中表达，也在与 PCa 相关的基质中表达，包括浸润的巨噬细胞。巨噬细胞在 PCa 的发生和发展中具有决定性的作用，但 AR 在巨噬细胞中的作用在很大程度上仍未被探索。在这里，我们表明，巨噬细胞样 THP-1 细胞系中的 AR 信号通路通过增加髓系细胞表达的触发受体-1（TREM-1）信号通路和其下游细胞因子的表达，支持 PCa 细胞系在培养中的迁移和侵袭。此外，THP-1 和单核细胞来源的巨噬细胞中的 AR 信号通路上调了白细胞介素-10 和组织驻留标志物。总之，我们的数据表明，巨噬细胞中的 AR 信号通路可能支持 PCa 的侵袭性，阻断这一过程可能是抗雄激素治疗的一种机制。