Immature Low-Density Neutrophils Exhibit Metabolic Flexibility that Facilitates Breast Cancer Liver Metastasis
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 neut...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-06-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719307302 |
| _version_ | 1819194678751264768 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Brian E. Hsu |
| collection | DOAJ |
| description | 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 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 flexibility, NETosis |
| first_indexed | 2024-12-23T02:00:41Z |
| format | Article |
| id | doaj.art-25f477ee241a49fb82076fe716b1a056 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-23T02:00:41Z |
| publishDate | 2019-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-25f477ee241a49fb82076fe716b1a0562022-12-21T18:03:59ZengElsevierCell Reports2211-12472019-06-01271339023915.e6Immature Low-Density Neutrophils Exhibit Metabolic Flexibility that Facilitates Breast Cancer Liver MetastasisBrian E. Hsu0Sébastien Tabariès1Radia M. Johnson2Sylvia Andrzejewski3Julien Senecal4Camille Lehuédé5Matthew G. Annis6Eric H. Ma7Sandra Völs8LeeAnn Ramsay9Remi Froment10Anie Monast11Ian R. Watson12Zvi Granot13Russell G. Jones14Julie St-Pierre15Peter M. Siegel16Goodman Cancer Research Centre, McGill University, Montreal, Québec, QC H3A 1A3, Canada; Department of Medicine, McGill University, Montreal, Québec, QC H3G 1Y6, CanadaGoodman Cancer Research Centre, McGill University, Montreal, Québec, QC H3A 1A3, CanadaGenentech, 1 DNA Way South, San Francisco, CA 94080, USAGoodman Cancer Research Centre, McGill University, Montreal, Québec, QC H3A 1A3, CanadaGoodman Cancer Research Centre, McGill University, Montreal, Québec, QC H3A 1A3, Canada; Department of Medicine, McGill University, Montreal, Québec, QC H3G 1Y6, CanadaGoodman Cancer Research Centre, McGill University, Montreal, Québec, QC H3A 1A3, CanadaGoodman Cancer Research Centre, McGill University, Montreal, Québec, QC H3A 1A3, CanadaGoodman Cancer Research Centre, McGill University, Montreal, Québec, QC H3A 1A3, Canada; Department of Physiology, McGill University, Montreal, Québec, QC H3G 1Y6, CanadaDepartment of Developmental Biology and Cancer Research, Hebrew University-Hadassah Medical School, Jerusalem, IsraelGoodman Cancer Research Centre, McGill University, Montreal, Québec, QC H3A 1A3, CanadaDepartment of Pathology and Microbiology, Université de Montréal, Saint Hyacinth, Québec, QC J2S 2M2, CanadaGoodman Cancer Research Centre, McGill University, Montreal, Québec, QC H3A 1A3, CanadaGoodman Cancer Research Centre, McGill University, Montreal, Québec, QC H3A 1A3, CanadaDepartment of Developmental Biology and Cancer Research, Hebrew University-Hadassah Medical School, Jerusalem, IsraelGoodman Cancer Research Centre, McGill University, Montreal, Québec, QC H3A 1A3, Canada; Department of Physiology, McGill University, Montreal, Québec, QC H3G 1Y6, CanadaDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, CanadaGoodman Cancer Research Centre, McGill University, Montreal, Québec, QC H3A 1A3, Canada; Department of Medicine, McGill University, Montreal, Québec, QC H3G 1Y6, Canada; Corresponding authorSummary: 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. : 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 flexibility, NETosishttp://www.sciencedirect.com/science/article/pii/S2211124719307302 |
| spellingShingle | 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 Immature Low-Density Neutrophils Exhibit Metabolic Flexibility that Facilitates Breast Cancer Liver Metastasis Cell Reports |
| title | Immature Low-Density Neutrophils Exhibit Metabolic Flexibility that Facilitates Breast Cancer Liver Metastasis |
| title_full | Immature Low-Density Neutrophils Exhibit Metabolic Flexibility that Facilitates Breast Cancer Liver Metastasis |
| title_fullStr | Immature Low-Density Neutrophils Exhibit Metabolic Flexibility that Facilitates Breast Cancer Liver Metastasis |
| title_full_unstemmed | Immature Low-Density Neutrophils Exhibit Metabolic Flexibility that Facilitates Breast Cancer Liver Metastasis |
| title_short | Immature Low-Density Neutrophils Exhibit Metabolic Flexibility that Facilitates Breast Cancer Liver Metastasis |
| title_sort | immature low density neutrophils exhibit metabolic flexibility that facilitates breast cancer liver metastasis |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719307302 |
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