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Publication : Androgens drive sexual dimorphism in liver metastasis by promoting hepatic accumulation of neutrophils.

First Author  Tang JJ Year  2022
Journal  Cell Rep Volume  39
Issue  12 Pages  110987
PubMed ID  35732131 Mgi Jnum  J:326728
Mgi Id  MGI:7295275 Doi  10.1016/j.celrep.2022.110987
Citation  Tang JJ, et al. (2022) Androgens drive sexual dimorphism in liver metastasis by promoting hepatic accumulation of neutrophils. Cell Rep 39(12):110987
abstractText  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 dimorphism in LM (SDLM) and the underlying mechanisms remain unclear. We herein demonstrate a significant male-biased SDLM, which is attributed to host androgen/androgen receptor (Ar) signaling that promotes hepatic seeding of tumor cells and subsequent outgrowth in a neutrophil-dependent manner. Mechanistically, androgen/Ar signaling promotes 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 mitigates 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.
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