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

被引：1320

作者：

Albrengues, Jean ^{[1
]}

Shields, Mario A. ^{[1
]}

Ng, David ^{[1
]}

Park, Chun Gwon ^{[2
,3
]}

Ambrico, Alexandra ^{[1
]}

Poindexter, Morgan E. ^{[4
]}

Upadhyay, Priya ^{[4
]}

Uyeminami, Dale L. ^{[4
]}

Pommier, Arnaud ^{[1
]}

Kuttner, Victoria ^{[1
]}

Bruzas, Emilis ^{[1
,5
]}

Maiorino, Laura ^{[1
,5
]}

Bautista, Carmelita ^{[1
]}

Carmona, Ellese M. ^{[2
,3
]}

Gimotty, Phyllis A. ^{[6
]}

Fearon, Douglas T. ^{[1
,7
,8
]}

Chang, Kenneth ^{[1
]}

Lyons, Scott K. ^{[1
]}

Pinkerton, Kent E. ^{[4
]}

Trotman, Lloyd C. ^{[1
]}

Goldberg, Michael S. ^{[2
,3
]}

Yeh, Johannes T. -H. ^{[1
]}

Egeblad, Mikala ^{[1
]}

机构：

[1] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA

[2] Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02215 USA

[3] Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02215 USA

[4] Univ Calif Davis, Ctr Hlth & Environm, Davis, CA 95616 USA

[5] Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA

[6] Univ Penn, Perelman Sch Med, Dept Biostat Epidemiol & Informat, Philadelphia, PA 19104 USA

[7] Univ Cambridge, Canc Res UK, Cambridge Inst, Li Ka Shing Ctr, Cambridge CB2 0RE, England

[8] Weill Cornell Med Coll, Meyer Canc Ctr, New York, NY 10021 USA

来源：

SCIENCE | 2018年 / 361卷 / 6409期

关键词：

TUMOR-CELLS; MATRIX METALLOPROTEINASES; UROKINASE RECEPTOR; BONE-MARROW; PROMOTE; GROWTH; METASTASIS; INHIBITION; MECHANISMS; ELASTASE;

D O I：

10.1126/science.aao4227

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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 a3b1 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. © 2018 American Association for the Advancement of Science. All rights reserved.

引用

页码：1353 / +

页数：14

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