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Early neutrophilia marked by aerobic glycolysis sustains host 3 metabolism and delays cancer cachexia
File(s)
cancers-14-00963-v2.pdf (3.12 MB)
Published version
OA Location
Author(s)
Petruzzelli, Michele
Ferrer, Miriam
Schuijs, Martijn J
Kleeman, Sam O
Mourikis, Nicholas
Type
Journal Article
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.
Date Issued
2022-02-15
Date Acceptance
2022-02-09
Citation
Cancers, 2022, 14 (4)
URI
DOI
ISSN
2072-6694
Publisher
MDPI AG
Journal / Book Title
Cancers
Volume
14
Issue
4
Copyright Statement
© 2022 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
License URL
Subjects
aerobic glycolysis
cachexia
cancer
host
metabolism
neutrophils
1112 Oncology and Carcinogenesis
Publication Status
Published
Article Number
ARTN 963