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

• DOI: 10.1016/j.celrep.2019.05.091
• Publication Date: 2019-06-25T15:28:31Z
• Authors: Brian E. Hsu; Sébastien Tabariès; Radia M. Johnson; Sylvia Andrzejewski; Julien Senecal; Camille Lehuédé; Matthew G. Annis; Eric H. Ma; Sandra Völs; LeeAnn Ramsay; Remi Froment; Anie Monast; Ian R. Watson; Zvi Granot; Russell G. Jones; Julie St-Pierre; Peter M. Siegel
• Keywords: Catabolism; Liver Cancer; Metabolome; Bioenergetics

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) promote liver metastasis. In contrast, mature high-density inhibit the formation of metastases. Transcriptomic metabolomic analyses high- reveal engagement numerous metabolic pathways specifically in neutrophils. iLDNs exhibit enhanced global bioenergetic capacity, through their ability engage mitochondrial-dependent ATP production, remain capable executing neutrophil functions, including NETosis, under nutrient-deprived conditions. demonstrate NETosis an important function promotes breast cancer rely on catabolism glutamate proline support metabolism absence glucose, which enables sustained NETosis. These data distinct populations a high degree flexibility, facilitates