@article{b6785e4435434c7c9111a28e9bb3fbef,
title = "Lung mesenchymal cells elicit lipid storage in neutrophils that fuel breast cancer lung metastasis",
abstract = "Acquisition of a lipid-laden phenotype by immune cells has been defined in infectious diseases and atherosclerosis but remains largely uncharacterized in cancer. Here, in breast cancer models, we found that neutrophils are induced to accumulate neutral lipids upon interaction with resident mesenchymal cells in the premetastatic lung. Lung mesenchymal cells elicit this process through repressing the adipose triglyceride lipase (ATGL) activity in neutrophils in prostaglandin E2-dependent and -independent manners. In vivo, neutrophil-specific deletion of genes encoding ATGL or ATGL inhibitory factors altered neutrophil lipid profiles and breast tumor lung metastasis in mice. Mechanistically, lipids stored in lung neutrophils are transported to metastatic tumor cells through a macropinocytosis–lysosome pathway, endowing tumor cells with augmented survival and proliferative capacities. Pharmacological inhibition of macropinocytosis significantly reduced metastatic colonization by breast tumor cells in vivo. Collectively, our work reveals that neutrophils serve as an energy reservoir to fuel breast cancer lung metastasis.",
author = "Peishan Li and Ming Lu and Jiayuan Shi and Zheng Gong and Li Hua and Qing Li and Bora Lim and Zhang, {Xiang H.F.} and Xiaowen Chen and Sheng Li and Shultz, {Leonard D.} and Guangwen Ren",
note = "Funding Information: We thank S.I. Abrams (Roswell Park Comprehensive Cancer Center) for providing the AT3 breast cancer cell line, Y. Kang (Princeton University) for providing the MDA-4175 breast cancer cell line and R.A. Weinberg (Whitehead Institute for Biomedical Research) for providing the lentiviralvector expressing mouse Csf3. This work was supported by grants from the National Institutes of Health (R00-CA188093 to G.R.; R37-CA237307 to G.R.; P30-CA034196 to G.R., L.D.S. and S.L.; R35−GM133562 to S.L.; and R24-OD026440 and R01-AI132963 to L.D.S.), the U.S. Department of Defense (W81XWH-18-1-0013 to G.R.), Leukemia Research Foundation New Investigator Grant (to S.L.) and The Jackson Laboratory Director{\textquoteright}s Innovation Fund (19000-17-31 to S.L.). Q.L. is supported by the Pyewacket Fund at The Jackson Laboratory. We acknowledge critical comments from E. T. Liu, N. A. Rosenthal, K. Seburn and C. Robinett. We also thank G. Stafford for RNA-seq analysis and W. Schott for cell sorting, as well as The Jackson Laboratory Scientific Service for assistance. Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2020",
month = nov,
day = "1",
doi = "10.1038/s41590-020-0783-5",
language = "English (US)",
volume = "21",
pages = "1444--1455",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "11",
}