Immature Low-Density Neutrophils Exhibit Metabolic Flexibility that Facilitates Breast Cancer Liver Metastasis

Immature Low-Density Neutrophils Exhibit Metabolic Flexibility that Facilitates Breast Cancer Liver Metastasis

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Summary: 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 china glaze holee shift 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.: Hsu et al.demonstrate that tumor-derived G-CSF, in concert with additional factors, mobilizes immature low-density neutrophils (iLDNs) that promote breast cancer liver metastasis.

iLDNs are able to perform pro-metastatic functions under metabolically challenging conditions, such as low glucose, due to their enhanced global bioenergetic capacity.Keywords: neutrophil plasticity, metastasis, metabolic sombrero de los 2 carnales flexibility, NETosis.