Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice.
Science
; 361(6409)2018 09 28.
Article
en En
| MEDLINE
| ID: mdl-30262472
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 α3ß1 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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Neumonía
/
Laminas
/
Carcinogénesis
/
Trampas Extracelulares
/
Neoplasias Pulmonares
/
Neutrófilos
Tipo de estudio:
Etiology_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Science
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos