Lung mesenchymal cells elicit lipid storage in neutrophils that fuel breast cancer lung metastasis
| Autor: | Leonard D. Shultz, Li Hua, Bora Lim, Xiang Zhang, Qing Li, Zheng Gong, Sheng Li, Xiaowen Chen, Guangwen Ren, Jiayuan Shi, Mingyang Lu, Peishan Li |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Lung Neoplasms Neutrophils Immunology Fluorescent Antibody Technique Breast Neoplasms Article Mice 03 medical and health sciences 0302 clinical medicine Breast cancer Immune system Animals Humans Immunology and Allergy Medicine Neoplasm Metastasis Cell Proliferation Lung business.industry Cell growth Mesenchymal stem cell Cancer Mesenchymal Stem Cells Lipid metabolism Lipid Metabolism medicine.disease Endocytosis 030104 developmental biology medicine.anatomical_structure Adipose triglyceride lipase Disease Progression Cancer research Female business Biomarkers 030215 immunology |
| Zdroj: | Nature immunology |
| ISSN: | 1529-2916 1529-2908 |
| DOI: | 10.1038/s41590-020-0783-5 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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