김현호 (고려대학교)

한빛사논문

조회852

고려대학교

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Adv. Sci., First published: 03 June 2022 | https://doi.org/10.1002/advs.202201785 Recapitulated Crosstalk between Cerebral Metastatic Lung Cancer Cells and Brain Perivascular Tumor Microenvironment in a Microfluidic Co-Culture Chip

Hyunho Kim, Jason K. Sa, Jaehoon Kim, Hee Jin Cho, Hyun Jeong Oh, Dong-Hee Choi, Seok-Hyeon Kang, Da Eun Jeong, Do-Hyun Nam, Hakho Lee, Hye Won Lee,* and Seok Chung*

H. Kim, J. Kim, H. J. Oh, D.-H. Choi, S.-H. Kang, S. Chung
School of Mechanical Engineering, College of Engineering Korea University Seoul 02841, Republic of Korea

H. Kim, H. Lee
Center for Systems Biology Massachusetts General Hospital Boston, MA 02114, USA

J. K. Sa
Department of Biomedical Sciences Korea University College of Medicine Seoul 02841, Republic of Korea

J. Kim
George W. Woodruff School of Mechanical Engineering Georgia Institute of Technology Atlanta, GA 30332, USA

H. J. Cho
Department of Biomedical Convergence Science and Technology Kyungpook National University Daegu 41566, Republic of Korea

H. J. Cho
Cell and Matrix Research Institute Kyungpook National University Daegu 41944, Republic of Korea

D. E. Jeong
Bioscience division, Life Sciences and Laboratory Products Group Thermo Fisher Scientific Solutions Seoul 06349, Republic of Korea

D.-H. Nam
Institute for Refractory Cancer Research Samsung Medical Center Seoul 06351, Republic of Korea

D.-H. Nam
Department of Health Science & Technology, Samsung Advanced Institute for Health Sciences & Technology (SAIHST) Sungkyunkwan University Seoul 06351, Republic of Korea

D.-H. Nam
Department of Neurosurgery, Samsung Medical Center Sungkyunkwan University School of Medicine Seoul 06351, Republic of Korea

H. W. Lee
Department of Urology, Center for Urologic Cancer National Cancer Center Goyang 10408, Republic of Korea

S. Chung
KU-KIST Graduate School of Converging Science and Technology Korea University Seoul 02841, Republic of Korea

H.K. and J.K.S. contributed equally to this work.

Abstract

Non-small cell lung carcinoma (NSCLC), which affects the brain, is fatal and resistant to anti-cancer therapies. Despite innate, distinct characteristics of the brain from other organs, the underlying delicate crosstalk between brain metastatic NSCLC (BM-NSCLC) cells and brain tumor microenvironment (bTME) associated with tumor evolution remains elusive. Here, a novel 3D microfluidic tri-culture platform is proposed for recapitulating positive feedback from BM-NSCLC and astrocytes and brain-specific endothelial cells, two major players in bTME. Advanced imaging and quantitative functional assessment of the 3D tri-culture model enable real-time live imaging of cell viability and separate analyses of genomic/molecular/secretome from each subset. Susceptibility of multiple patient-derived BM-NSCLCs to representative targeted agents is altered and secretion of serpin E1, interleukin-8, and secreted phosphoprotein 1, which are associated with tumor aggressiveness and poor clinical outcome, is increased in tri-culture. Notably, multiple signaling pathways involved in inflammatory responses, nuclear factor kappa-light-chain-enhancer of activated B cells, and cancer metastasis are activated in BM-NSCLC through interaction with two bTME cell types. This novel platform offers a tool to elucidate potential molecular targets and for effective anti-cancer therapy targeting the crosstalk between metastatic cancer cells and adjacent components of bTME.

논문정보

형식Research article
게재일2022년 06월 (BRIC 등록일 2022-07-15)
연구진국내(교신)+국외 연구진
분야 의약학 > 응용의학

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