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Single-cell RNA transcriptome sequencing revealed that androgen/AR signaling promotes neutrophil precursors proliferation in bone marrow

ABSTRACT: The liver is one of the most-favored distant metastatic sites for solid tumors, and interactions between cancer cells and components of the hepatic microenvironment are essential for liver metastasis (LM). Although sex is one of the determinants for primary liver cancer, sexual disparity/dimorphism in LM (SDLM) and the underlying mechanisms remain unclear. We herein demonstrated a significant male-biased SDLM, which was attributed to host androgen/androgen receptor (AR) signaling that promoted hepatic seeding of tumor cells and subsequent outgrowth in a neutrophil-dependent manner. Mechanistically, androgen/AR signaling promoted hepatic accumulation of neutrophils by promoting proliferation and development of neutrophil precursors in the bone marrow, as well as modulating hepatic recruitment of neutrophils and their functions. Antagonizing the androgen/AR/neutrophil axis significantly mitigated LM in males. Our data thus reveal an important role of androgen in LM and suggest that androgen/AR modulation represents a promising target for LM therapy in men.

ORGANISM(S): Mus musculus

PROVIDER: GSE198175 | GEO | 2022/03/12

REPOSITORIES: GEO

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