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

URL: https://www.ncbi.nlm.nih.gov/pubmed/30262472
DOI: 10.1126/science.aao4227

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
organs, tissues, organelles, cell types and functions > organs types and functions > lung
diseases & disorders > cancer > metastasis
CSHL Authors:
Communities: CSHL labs > Chang lab
CSHL labs > Egeblad lab
CSHL labs > Fearon lab
CSHL labs > Krainer lab
CSHL labs > Lyons lab
CSHL labs > Trotman lab
Watson School > Publications
Northwell Health
Depositing User: Matthew Dunn
Date: 28 September 2018
Date Deposited: 18 Oct 2018 16:09
Last Modified: 11 Jan 2019 20:00
Related URLs:
URI: http://repository.cshl.edu/id/eprint/37261

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