Design and Construction of a Multi-Organ Microfluidic Chip Mimicking the in vivo Microenvironment of Lung Cancer Metastasis
Abstract
Metastasis is a complex pathophysiological process. As the main cause of cancer mortality in humans it represents a serious challenge to both basic researchers and clinicians. Here we report the design and construction of a multi-organ microfluidic chip that closely mimics the in vivo microenvironment of lung cancer metastasis. This multi-organs-on-a-chip includes an upstream "lung" and three downstream "distant organs", with three polydimethylsiloxane (PDMS) layers and two thin PDMS microporous membranes bonded to form three parallel microchannels. Bronchial epithelial, lung cancer, microvascular endothelial, mononuclear, and fibroblast cells were grown separated by the biomembrane in upstream "lung", while astrocytes, osteocytes, and hepatocytes were grown in distant chambers, to mimic lung cancer cell metastasis to the brain, bone, and liver. After culture in this system, lung cancer cells formed a "tumor mass", showed epithelial-mesenchymal transition (with altered expression of E-cadherin, N-cadherin, Snail1, and Snail2) and invasive capacity. A549 cells co-cultured with astrocytes overexpressed CXCR4 protein, indicating damage of astrocytes after cancer cell metastasis to the brain. Osteocytes overexpressed RANKL protein indicates damage of osteocytes after cancer cell metastasis to the bone, and hepatocytes overexpressed AFP protein indicates damage to hepatocytes after cancer cell metastasis to the liver. Finally, in vivo imaging of cancer growth and metastasis in a nude mice model validated the performance of metastasis in the organs-on-chip system. This system provides a useful tool to mimic the in vivo microenvironment of cancer metastasis and to investigate cell-cell interactions during metastasis.
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Wang's group used a multiorgan-on-a-chip platform consisting of one upstream lung and three downstream brain, bone, and liver organs to simulate lung cancer metastasis to brain, bone, and liver.
“Wang’s group took advantage of another multiorgan-on-a-chip platform to study lung cancer metastasis (Fig. 7e)225. The system consists of four organs: one upstream lung and three downstream parallel brain, bone, and liver organs. This model simulated the metastasis of lung cancer to the brain, bone, and liver.”
From Tumor-on-a-chip: from bioinspired design to biomedical application (2021) · cites this paper as [225]
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- Authors
- Xu, Z., Li, E., Guo, Z., Yu, R., Hao, H., Xu, Y., Sun, Z., Li, X., Lyu, J., & Wang, Q.
- Affiliations
- Shandong University (CN)
- Dalian Medical University (CN)
- First Affiliated Hospital of Dalian Medical University (CN)
- Wenzhou Medical University (CN)
- Corresponding author
- Lyu, Jianxin
- Wang, Qi
- Venue
- ACS Applied Materials & Interfaces
- Publisher
- American Chemical Society (ACS)
- Published
- 2016-09-20
- Volume
- 8
- Issue
- 39
- Pages
- 25840-25847
- ISSN
- 1944-8244 (ISSN-L)
- 1944-8252
- OpenAlex
- W2512537564
- Cited by
- 264
- References
- 27
- Citations by year
- 2026: 19 · 2025: 31 · 2024: 40 · 2023: 28 · 2022: 38 · 2021: 29 · 2020: 34 · 2019: 18 · 2018: 12 · 2017: 14
- FWCI
- 7.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- ACS Applied Materials & Interfaces (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Science and Technology of the People's Republic of China (2015AA020409)
- National Natural Science Foundation of China (81330060, 91129733)
- Zhejiang Province (LKFyc05)
- Science and Technology Plan Foundation of Liaoning Province (2014225003)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- multi-organ-on-a-chip, lung cancer metastasis, organotypic co-culture, epithelial-mesenchymal transition, tumor invasion, astrocyte damage, hepatocyte injury, CXCR4, RANKL, alpha-fetoprotein, A549 cells, cell-cell interactions, in vivo imaging
- MeSH terms
- Animals, Humans, Lung, Lung Neoplasms, Mice, Nude, Neoplasm Metastasis, Microfluidics, Cell Line, Tumor, Mice, Epithelial-Mesenchymal Transition, Tumor Microenvironment
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