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| Status |
Public on Jun 26, 2019 |
| Title |
Immature low-density neutrophils exhibit metabolic flexibility that facilitates breast cancer liver metastasis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Neutrophils play a key role in the control of metastatic progression. Neutrophils are phenotypically heterogeneous and can exert either anti- or pro-metastatic functions. Here, we demonstrate that tumor cells capable of forming liver metastases induce an accumulation of neutrophils in the peripheral blood and liver parenchyma. Cancer cell-derived G-CSF, in concert with other factors, mobilizes immature low-density neutrophils 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. Low-density neutrophils 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. Together, these data reveal that distinct pro-metastatic neutrophil populations exhibit a high degree of metabolic flexibility, which facilitates metastatic progression and the formation of liver metastases.
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| Overall design |
4 samples of Naïve neutrophils (bone marrow), 4 samples HDNs (from peripheral blood of liver metastasis bearing mice), 4 samples LDNs (from peripheral blood of liver metastasis bearing mice)
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| Contributor(s) |
Siegel P, Hsu B |
| Citation(s) |
31242422 |
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| Submission date |
Dec 11, 2018 |
| Last update date |
Oct 08, 2019 |
| Contact name |
Brian Hsu |
| E-mail(s) |
brian.hsu@mail.mcgill.ca
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| Phone |
5149935989
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| Organization name |
McGill University
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| Department |
Medicine
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| Lab |
Peter Siegel
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| Street address |
1160 Pine Avenue West
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| City |
Montréal |
| State/province |
QC |
| ZIP/Postal code |
H3A1A3 |
| Country |
Canada |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA509476 |
| SRA |
SRP173308 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE123669_HDN_vs_Naive_DEG.csv.gz |
774.7 Kb |
(ftp)(http) |
CSV |
| GSE123669_LDN_vs_GSE123669_HDN_DEG.csv.gz |
760.6 Kb |
(ftp)(http) |
CSV |
| GSE123669_LDN_vs_Naive_DEG.csv.gz |
769.1 Kb |
(ftp)(http) |
CSV |
| GSE123669_Neutrophil_Cnts_070109.csv.gz |
382.1 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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