Neutrophil extracellular traps produced during inflammation awakendormant cancer cells in mice

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 Corresponding author. [email protected]. Author contributions: J.A. and M.E. designed and directed the project. J.A. and D.N. performed all experiments, except as follow: M.E.P., P.U., D.L.U., and K.E.P. performed tobacco smoke exposure experiments on mice; A.A. and L.C.T. designed and performed experiments on RapidCaP mice; C.B. and J.T-H.Y. generated antibodies against cleaved murine laminin-111. C.G.P., E.M.C., and M.S.G. generated DNase I and free coated nanoparticles. A.P. and D.T.F. designed and performed flow cytometry experiments. K.C. generated the viral particles for shRNA mediated inducible knockdown of Integrin β1, FAK, MLCK and YAP. M.A.S. performed confocal intravital lung imaging. E.B., L.M. and V.K. generated reagents and/or helped analyze data. S.K.L. provided the FUCCI cell cycle reporter plasmid. P.A.G., J.A. and M.E. performed statistical analysis. J.A. and M.E. wrote the manuscript. Competing interests:D.T.F. is a Co-Founder of Myosotis LLC (a company developing cancer immunotherapies) and is on the Scientific Advisory Boards of iTEOS Therapeutics (a company developing immuno-oncology drugs), IFM Therapeutics, LLC (a company developing therapies targeting the innate immune system), and Kymab (a company developing therapeutic antibodies). The authors declare no other competing interests. Data and materials availability: All data are available in the main text or the supplementary materials. The Ab28 monoclonal antibody against cleaved laminin is available upon signing a Material Transfer Agreement. HHS Public Access Author manuscript Science. Author manuscript; available in PMC 2019 October 04. Published in final edited form as: Science. 2018 September 28; 361(6409): . doi:10.1126/science.aao4227. A uhor M anscript