Functional Investigation of NCI-H460-Inducible Myofibroblasts on the Chemoresistance to VP-16 with a Microfluidic 3D Co-Culture Device
Open accessAbstract
Fibroblasts, the major cell type in tumor stroma, are essential for tumor growth and survival, and represent an important therapeutic target for cancers. Here we presented a microfluidic co-culture device in which the three-dimensional (3D) matrix was employed to reconstruct an in vivo-like fibroblast-tumor cell microenvironment for investigation of the role of myofibroblasts induced by lung cancer cells in the chemoresistance to VP-16. Composed of a double-layer chip and an injection pump, the device houses fibroblasts and lung cancer cells co-cultured in 3D matrix and 2D mode to induce fibroblasts to become myofibroblasts with the supplement of the medium continuously. With this device, we verified that the cytokines secreted by lung cancer cells could effectively transform the fibroblasts into myofibroblasts. Moreover, compared to fibroblasts, the myofibroblasts showed higher resistance to anticancer drug VP-16. We also demonstrated that this kind of acquired resistance in myofibroblasts was associated with the expression of Glucose-regulated protein 78 (GP78). We concluded that this device allows for the assay to characterize various cellular events in a single device sequentially, facilitating a better understanding of the interactions among heterotypic cells in a sophisticated microenvironment.
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Many aspects of cancer biology have been studied in microfluidic systems in which cancerous cells are cultured under well-controlled conditions.
“Many aspects of the biology of cancer have been studied in microfluidic systems in which cancerous cells (frequently co-cultured with non-cancerous cells) are cultured under well-controlled conditions [8,105,106,107,108].”
From The Tumor-on-Chip: Recent Advances in the Development of Microfluidic Systems to Recapitulate the Physiology of Solid Tumors (2019) · cites this paper as [106]
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- Authors
- Hao, Y., Zhang, L., He, J., Guo, Z., Ying, L., Xu, Z., Zhang, J., Lu, J., & Wang, Q.
- Affiliations
- Dalian Medical University (CN)
- Affiliated Zhongshan Hospital of Dalian University (CN)
- Wenzhou Medical University (CN)
- Corresponding author
- Lu, Jianxin
- Wang, Qi
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-04-16
- Volume
- 8
- Issue
- 4
- Pages
- e61754
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3629031
- OpenAlex
- W2008358748
- Cited by
- 20
- References
- 40
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 5 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 5
- FWCI
- 1.07
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (973 Program, 81071228, 2012CB822103, #91129733)
- National Key Research and Development Program of China (2012CB822103)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- myofibroblasts, chemoresistance, etoposide, NCI-H460, lung cancer, tumor stroma, gp78, heterotypic cell interactions, tumor microenvironment
- MeSH terms
- Cell Line, Etoposide, Fibroblasts, Humans, Coculture Techniques, Microfluidics, Myofibroblasts
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