Early Neutrophilia Marked by Aerobic Glycolysis Sustains Host Metabolism and Delays Cancer Cachexia.
Authors
Petruzzelli, Michele
Schuijs, Martijn J
Kleeman, Sam O
Mourikis, Nicholas
Hall, Zoe
Perera, David
Raghunathan, Shwethaa
Lukey, Michael J
Frezza, Christian
Wagner, Erwin F
Venkitaraman, Ashok R
Janowitz, Tobias
Publication Date
2022-02-15Journal Title
Cancers (Basel)
ISSN
2072-6694
Publisher
MDPI AG
Volume
14
Issue
4
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Petruzzelli, M., Ferrer, M., Schuijs, M. J., Kleeman, S. O., Mourikis, N., Hall, Z., Perera, D., et al. (2022). Early Neutrophilia Marked by Aerobic Glycolysis Sustains Host Metabolism and Delays Cancer Cachexia.. Cancers (Basel), 14 (4) https://doi.org/10.3390/cancers14040963
Abstract
An elevated neutrophil-lymphocyte ratio negatively predicts the outcome of patients with cancer and is associated with cachexia, the terminal wasting syndrome. Here, using murine model systems of colorectal and pancreatic cancer we show that neutrophilia in the circulation and multiple organs, accompanied by extramedullary hematopoiesis, is an early event during cancer progression. Transcriptomic and metabolic assessment reveals that neutrophils in tumor-bearing animals utilize aerobic glycolysis, similar to cancer cells. Although pharmacological inhibition of aerobic glycolysis slows down tumor growth in C26 tumor-bearing mice, it precipitates cachexia, thereby shortening the overall survival. This negative effect may be explained by our observation that acute depletion of neutrophils in pre-cachectic mice impairs systemic glucose homeostasis secondary to altered hepatic lipid processing. Thus, changes in neutrophil number, distribution, and metabolism play an adaptive role in host metabolic homeostasis during cancer progression. Our findings provide insight into early events during cancer progression to cachexia, with implications for therapy.
Keywords
cancer, cachexia, metabolism, host, neutrophils, aerobic glycolysis
Sponsorship
Medical Research Council (MC_UU_12022/1)
MRC (MC_UU_12022/8)
Wellcome Trust (204622/Z/16/Z)
Medical Research Council (MC_UU_12022/6)
Identifiers
External DOI: https://doi.org/10.3390/cancers14040963
This record's URL: https://www.repository.cam.ac.uk/handle/1810/334144
Rights
Licence:
https://creativecommons.org/licenses/by/4.0/
Statistics
Total file downloads (since January 2020). For more information on metrics see the
IRUS guide.
Recommended or similar items
The current recommendation prototype on the Apollo Repository will be turned off on 03 February 2023. Although the pilot has been fruitful for both parties, the service provider IKVA is focusing on horizon scanning products and so the recommender service can no longer be supported. We recognise the importance of recommender services in supporting research discovery and are evaluating offerings from other service providers. If you would like to offer feedback on this decision please contact us on: support@repository.cam.ac.uk