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Recapitulated Crosstalk between Cerebral Metastatic Lung Cancer Cells and Brain Perivascular Tumor Microenvironment in a Microfluidic Co-Culture Chipopen access

Authors
Kim, HyunhoSa, Jason K.Kim, JaehoonCho, Hee JinOh, Hyun JeongChoi, Dong-HeeKong, Seok-HyeonJeong, Da EunNam, Do-HyunLee, HakhoLee, Hye WonChung, Seok
Issue Date
8월-2022
Publisher
WILEY
Keywords
brain perivascular tumor microenvironment; cerebral metastatic lung cancer cells; microfluidic co-culture chip
Citation
ADVANCED SCIENCE, v.9, no.22
Indexed
SCIE
SCOPUS
Journal Title
ADVANCED SCIENCE
Volume
9
Number
22
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/143232
DOI
10.1002/advs.202201785
ISSN
2198-3844
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.
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