Murine breast cancers disorganize the liver transcriptome in a zonated manner

• DOI: 10.1038/s42003-023-04479-w
• Publication Date: 2023-01-24T10:06:37Z
• Authors: Alexis Vandenbon; Rin Mizuno; Riyo Konishi; Masaya Onishi; Kyoko Masuda; Yuka Kobayashi; Hiroshi Kawamoto; Ayako Suzuki; Chenfeng He; Yuki Nakamura; Kosuke Kawaguchi; Masakazu Toi; Masahito Shimizu; Yasuhito Tanaka; Yutaka Suzuki; Shinpei Kawaoka
• Keywords: 0301 basic medicine; QH301-705.5; Gene Expression Profiling; Article; 3. Good health; Mice; 03 medical and health sciences; Breast cancer; Liver; Neoplasms; Hepatocytes; Animals; Homeostasis; Data integration; Biology (General); Cancer models; Transcriptome

AbstractThe spatially organized gene expression program within the liver specifies hepatocyte functions according to their relative distances to the bloodstream (i.e., zonation), contributing to liver homeostasis. Despite the knowledge that solid cancers remotely disrupt liver homeostasis, it remains unexplored whether solid cancers affect liver zonation. Here, using spatial transcriptomics, we thoroughly investigate the abundance and zonation of hepatic genes in cancer-bearing mice. We find that breast cancers affect liver zonation in various distinct manners depending on biological pathways. Aspartate metabolism and triglyceride catabolic processes retain relatively intact zonation patterns, but the zonation of xenobiotic catabolic process genes exhibits a strong disruption. The acute phase response is induced in zonated manners. Furthermore, we demonstrate that breast cancers activate innate immune cells in particular neutrophils in distinct zonated manners, rather than in a uniform fashion within the liver. Collectively, breast cancers disorganize hepatic transcriptomes in zonated manners, thereby disrupting zonated functions of the liver.