	성함(국문)	석 승 혁
	성함(영문)	Seung Hyeok Seok
	소속(국문)	서울대학교 의과대학 미생물학교실
	소속(영문)	Microbiology and Immunology, College of Med., Seoul National Univ.
	직위	교 수
	메일	lamseok@snu.ac.kr
학력 및 경력 (대학교 이상)
Educational Experience: 2001-2007 College of Vet Medicine, Seoul National Univ. (PhD) 1994-1998 College of Vet Medicine, Seoul National Univ. (DVM) Professional Experience: 2019-Current College of Medicine, Seoul National Univ. (Professor) 2014-209 College of Medicine, Seoul National Univ. (Associate professor) 2010-2013 College of Medicine, Seoul National Univ. (Assistant professor) 2008-2009 Institute for Biomedical Research, Seoul National Univ. Hospital (Clinical Professor)
대표논문 Chung H, Park JY, Kim K, Yoo RJ, Suh M, Gu GJ, Kim JS, Choi TH, Byun JW, Ju YW, Han W, Ryu HS, Chung G, Hwang DW, Kim Y, Kang HR, Na YR, Choi H, Im HJ, Lee YS, Seok SH *. Circulation Time-Optimized Albumin Nanoplatform for Quantitative Visualization of Lung Metastasis via Targeting of Macrophages. ACS Nano. 2022 Aug 23 (IF 18.03 Corresponding author) Na YR, Jung D, Stakenborg M, Jang H, Gu GJ, Jeong MR, Suh SY, Kim HJ, Kwon YH, Sung TS, Ryoo SB, Park KJ, Im JP, Lee YS, Han H, Park B, Lee S, Kim D, Lee HS, Cleynen I, Matteoli G*, Seok SH *. Prostaglandin E2 Receptor PTGER4-expressing macrophages promote intestinal epithelial barrier regeneration upon inflammation. Gut. 2021 Feb 8. (IF 31.793 Corresponding author) Na YR, Kwon JW, Kim DY, Chung H, Song J, Jung D, Quan H, Kim D, Kim JS, Ju YW, Han W, Ryu HS, Lee YS, Hong JJ, Seok SH *. Protein Kinase A Catalytic Subunit Is a Molecular Switch that Promotes the Pro-tumoral Function of Macrophages. Cell Rep. 2020 May 12;31(6) (IF 9.995 Corresponding author) Kim H, Chung H, Kim J, Choi DH, Shin Y, Kang YG, Kim BM, Seo SU, Chung S *, Seok SH *. Macrophages-triggered sequential remodeling of endothelium-interstitial matrix to form pre-metastatic niche in microfluidic tumor microenvironment. Advanced Science. 2019 Apr 10; 6(11) (IF 17.521 Corresponding author) Na YR, Stakenborg M, Seok SH*, Matteoli G*. Macrophages in intestinal inflammation and resolution: a potential therapeutic target in IBD. Nature Reviews Gastroenterology & Hepatology. 2019 Jul 16. Doi: 10.1038/s41575-019-0172-4 (IF 73.082 Corresponding author)

Tumoral activation of endothelium drives macrophages-mediated metastatic niche formation and promotes lung metastasis

Prof. Seung Hyeok Seok, DVM, PhD, DKCLAM

Macrophage Lab, Department of Microbiology and Immunology, and Institute of Endemic Disease, Seoul National University College of Medicine, Seoul, Republic of Korea

Abstract

Primary tumor induces macrophages-enriched environment to establish metastatic niche which enhances homing and colonization of circulating tumor cells. However, the molecular mechanism underlying endothelial remodeling that favors macrophages infiltration and subsequent niche formation is not fully understood. Here, we found that tumor-derived factors activated endothelial cells to increase adhesive efficacy of monocytes to the endothelium, leading to macrophage infiltration. In mouse models of pulmonary metastasis, this endothelial activation triggered formation of premetastatic niche via accumulation of macrophages in the lungs. Of note, macrophages primed the metastatic microenvironment through enhancing expression of niche-related genes including S100A8, S100A9, MMP9 and fibronectin within the premetastatic lungs and directly transmitted survival signal to tumor cells in a contact-dependent manner. Furthermore, we demonstrated that depletion of macrophages specifically during premetastatic stages reduced niche formation and also resulted in reduced metastatic burden. These findings suggest that endothelial remodeling at metastatic site is a key step for initiation of premetastatic niche formation supported by macrophages. Targeting this step could present an opportunity for therapeutic intervention of metastatic spread in patients with malignant cancers.