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• W2955177546 abstract "Neutrophils are phenotypically heterogeneous and exert either anti- or pro-metastatic functions. We show that cancer-cell-derived G-CSF is necessary, but not sufficient, to mobilize immature low-density neutrophils (iLDNs) that promote liver metastasis. In contrast, mature high-density neutrophils inhibit the formation of liver metastases. Transcriptomic and metabolomic analyses of high- and low-density neutrophils reveal engagement of numerous metabolic pathways specifically in low-density neutrophils. iLDNs exhibit enhanced global bioenergetic capacity, through their ability to engage mitochondrial-dependent ATP production, and remain capable of executing pro-metastatic neutrophil functions, including NETosis, under nutrient-deprived conditions. We demonstrate that NETosis is an important neutrophil function that promotes breast cancer liver metastasis. iLDNs rely on the catabolism of glutamate and proline to support mitochondrial-dependent metabolism in the absence of glucose, which enables sustained NETosis. These data reveal that distinct pro-metastatic neutrophil populations exhibit a high degree of metabolic flexibility, which facilitates the formation of liver metastases." @default.
• W2955177546 created "2019-07-12" @default.
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• W2955177546 date "2019-06-01" @default.
• W2955177546 modified "2023-10-15" @default.
• W2955177546 title "Immature Low-Density Neutrophils Exhibit Metabolic Flexibility that Facilitates Breast Cancer Liver Metastasis" @default.
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• W2955177546 doi "https://doi.org/10.1016/j.celrep.2019.05.091" @default.
• W2955177546 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31242422" @default.
• W2955177546 hasPublicationYear "2019" @default.
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