Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice

Albrengues, J., Shields, M. A., Ng, D., Park, C. G., Ambrico, A., Poindexter, M. E., Upadhyay, P., Uyeminami, D. L., Pommier, A., Kuttner, V., Bruzas, E., Maiorino, L., Bautista, C., Carmona, E. M., Gimotty, P. A., Fearon, D. T., Chang, K., Lyons, S. K., Pinkerton, K. E., Trotman, L. C., Goldberg, M. S., Yeh, J. T., Egeblad, M. (September 2018) Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice. Science, 361 (6409). ISSN 0036-8075

Abstract

Cancer cells from a primary tumor can disseminate to other tissues, remaining dormant and clinically undetectable for many years. Little is known about the cues that cause these dormant cells to awaken, resume proliferating, and develop into metastases. Studying mouse models, we found that sustained lung inflammation caused by tobacco smoke exposure or nasal instillation of lipopolysaccharide converted disseminated, dormant cancer cells to aggressively growing metastases. Sustained inflammation induced the formation of neutrophil extracellular traps (NETs), and these were required for awakening dormant cancer. Mechanistic analysis revealed that two NET-associated proteases, neutrophil elastase and matrix metalloproteinase 9, sequentially cleaved laminin. The proteolytically remodeled laminin induced proliferation of dormant cancer cells by activating integrin alpha3beta1 signaling. Antibodies against NET-remodeled laminin prevented awakening of dormant cells. Therapies aimed at preventing dormant cell awakening could potentially prolong the survival of cancer patients.

Item Type: Paper
Subjects: diseases & disorders > cancer
diseases & disorders
diseases & disorders > neoplasms
organism description > animal
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions
diseases & disorders > inflammation
organs, tissues, organelles, cell types and functions > organs types and functions > lung
organism description > animal > mammal
diseases & disorders > cancer > metastasis
organism description > animal > mammal > rodent > mouse
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neutrophils
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neutrophils
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neutrophils
organs, tissues, organelles, cell types and functions
organism description > animal > mammal > rodent > rat
organism description > animal > mammal > rodent > rat
organism description > animal > mammal > rodent
organs, tissues, organelles, cell types and functions > tissues types and functions > signal transduction
organs, tissues, organelles, cell types and functions > tissues types and functions
CSHL Authors:
Communities: CSHL Cancer Center Program > Cancer Genetics and Genomics Program
CSHL Cancer Center Program > Cellular Communication in Cancer Program
CSHL Cancer Center Shared Resources > Antibody and Phage Display Service
CSHL labs > Chang lab
CSHL labs > Egeblad lab
CSHL labs > Fearon lab
CSHL labs > Krainer lab
CSHL labs > Lyons lab
CSHL labs > Trotman lab
Northwell Health
School of Biological Sciences > Publications
CSHL Cancer Center Shared Resources > Animal Shared Resource
Depositing User: Matthew Dunn
Date: 28 September 2018
Date Deposited: 18 Oct 2018 16:09
Last Modified: 06 Feb 2024 20:47
PMCID: PMC6777850
Related URLs:
URI: https://repository.cshl.edu/id/eprint/37261

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