Neutrophil Extracellular Traps Produced During Inflammation Awaken Dormant Cancer Cells in Mice

Overview

Journal Science

Specialty Science

Date 2018 Sep 29

PMID 30262472

Citations 695

Authors

Jean Albrengues

Mario A Shields

David Ng

Chun Gwon Park

Alexandra Ambrico

Morgan E Poindexter

Priya Upadhyay

Dale L Uyeminami

Arnaud Pommier

Victoria Kuttner

Emilis Bruzas

Laura Maiorino

Carmelita Bautista

Ellese M Carmona

Phyllis A Gimotty

Douglas T Fearon

Kenneth Chang

Scott K Lyons

Kent E Pinkerton

Lloyd C Trotman

Michael S Goldberg

Johannes T-H Yeh

Mikala Egeblad

Affiliations

Soon will be listed here.

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 α3β1 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.

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