Chronic stress increases metastasis via neutrophil-mediated changes to the microenvironment

He, Xue-Yan, Gao, Yuan, Ng, David, Michalopoulou, Evdokia, George, Shanu, Adrover, Jose M, Sun, Lijuan, Albrengues, Jean, Daßler-Plenker, Juliane, Han, Xiao, Wan, Ledong, Wu, Xiaoli Sky, Shui, Longling S, Huang, Yu-Han, Liu, Bodu, Su, Chang, Spector, David L, Vakoc, Christopher R, Van Aelst, Linda, Egeblad, Mikala (February 2024) Chronic stress increases metastasis via neutrophil-mediated changes to the microenvironment. Cancer Cell. ISSN 1535-6108

Abstract

Chronic stress is associated with increased risk of metastasis and poor survival in cancer patients, yet the reasons are unclear. We show that chronic stress increases lung metastasis from disseminated cancer cells 2- to 4-fold in mice. Chronic stress significantly alters the lung microenvironment, with fibronectin accumulation, reduced T cell infiltration, and increased neutrophil infiltration. Depleting neutrophils abolishes stress-induced metastasis. Chronic stress shifts normal circadian rhythm of neutrophils and causes increased neutrophil extracellular trap (NET) formation via glucocorticoid release. In mice with neutrophil-specific glucocorticoid receptor deletion, chronic stress fails to increase NETs and metastasis. Furthermore, digesting NETs with DNase I prevents chronic stress-induced metastasis. Together, our data show that glucocorticoids released during chronic stress cause NET formation and establish a metastasis-promoting microenvironment. Therefore, NETs could be targets for preventing metastatic recurrence in cancer patients, many of whom will experience chronic stress due to their disease.

Item Type: Paper
Subjects: diseases & disorders > cancer
diseases & disorders
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell cycle > Neutrophil extracellular traps
diseases & disorders > cancer > cancer types > breast cancer
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell cycle
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions
organs, tissues, organelles, cell types and functions > cell types and functions
diseases & disorders > cancer > metastasis
organs, tissues, organelles, cell types and functions
diseases & disorders > cancer > cancer types
CSHL Authors:
Communities: CSHL Cancer Center Program
CSHL Cancer Center Program > Cancer Genetics and Genomics Program
CSHL Cancer Center Program > Cellular Communication in Cancer Program
CSHL Cancer Center Program > Gene Regulation and Inheritance Program
CSHL Cancer Center Shared Resources
CSHL Cancer Center Shared Resources > Animal Services
CSHL Cancer Center Shared Resources > Flow Cytometry Service
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 13 February 2024
Date Deposited: 28 Feb 2024 14:09
Last Modified: 01 Oct 2024 17:40
PMCID: PMC11300849
Related URLs:
URI: https://repository.cshl.edu/id/eprint/41446

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