Recapitulated Crosstalk between Cerebral Metastatic Lung Cancer Cells and Brain Perivascular Tumor Microenvironment in a Microfluidic Co‐Culture Chip. Issue 22 (3rd June 2022)

• Record Type: Journal Article
• Authors: Kim, Hyunho; Sa, Jason K.; Kim, Jaehoon; Cho, Hee Jin; Oh, Hyun Jeong; Choi, Dong‐Hee; Kang, Seok‐Hyeon; Jeong, Da Eun; Nam, Do‐Hyun; Lee, Hakho; Lee, Hye Won; Chung, Seok
• Is Part Of: Advanced science. Volume 9:Issue 22(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-06-03
• Subjects: brain perivascular tumor microenvironment -- cerebral metastatic lung cancer cells -- microfluidic co‐culture chip; Science -- Periodicals; 505
• DOI: 10.1002/advs.202201785
• Languages: English
• ISSNs: 2198-3844

Abstract

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. Abstract : The development of a microfluidic triculture chip to simulate interactions between brain metastatic tumor cells and the microenvironment of the brain tumor. The microfluidic chip allows for the cultivation of patient‐derived cells in complex components of reconstituted brain, as well as the spatial collection of conditioned media and cells for a variety of biological analyses. This innovative platform allows the screening of drugs that target the intercellular communication between metastatic cancer cells and microenvironmental components at the metastatic site.