한빛사 논문
Young-Min Hyun1,*, Sang-Uk Seo2,3,*, Woo Seon Choi4,5, Hyung-Joon Kwon4, Dong-Young Kim4, Soi Jeong1, Gyeong-Yi Kang1, Eunbi Yi4,5, Minjung Kim4, Hyun Jin Ryu4, Mark R. Looney6, Eun Young Choi4,† and Hun Sik Kim4,5,†
1Department of Anatomy and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.
2Mucosal Immunology Laboratory, University of Ulsan College of Medicine, Seoul, Republic of Korea.
3Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
4Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
5Stem Cell Immunomodulation Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
6Departments of Medicine and Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
†Corresponding author.
*These authors contributed equally to this work as first authors.
Abstract
Distant metastasis represents the primary cause of cancer-associated death. Pulmonary metastasis is most frequently seen in many cancers, largely driven by lung inflammation. Components from primary tumor or recruited leukocytes are known to facilitate metastasis formation. However, contribution of target site–specific host factor to metastasis is poorly understood. Here, we show that developmental endothelial locus–1 (DEL-1), an anti-inflammatory factor abundant in the lung and down-regulated by inflammatory insults, protects from melanoma lung metastasis independently of primary tumor development and systemic immunosurveillance. DEL-1 deficiency is associated with gene profiles that favor metastatic progression with inflammation and defective immunosurveillance. Mechanistically, DEL-1 deficiency primarily influences Ly6G+ neutrophil accumulation in lung metastatic niche, leading to IL-17A up-regulation from γδ T cells and reduced antimetastatic NK cells. In support, neutrophil depletion or recombinant DEL-1 treatment profoundly reverses these effects. Thus, our results identify DEL-1 as a previously unrecognized link between tumor-induced inflammation and pulmonary metastasis.
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