Therapy response testing of breast cancer in a 3D high-throughput perfused microfluidic platform
Open accessAbstract
BACKGROUND: Breast cancer is the most common invasive cancer among women. Currently, there are only a few models used for therapy selection, and they are often poor predictors of therapeutic response or take months to set up and assay. In this report, we introduce a microfluidic OrganoPlate® platform for extracellular matrix (ECM) embedded tumor culture under perfusion as an initial study designed to investigate the feasibility of adapting this technology for therapy selection. METHODS: The triple negative breast cancer cell lines MDA-MB-453, MDA-MB-231 and HCC1937 were selected based on their different BRCA1 and P53 status, and were seeded in the platform. We evaluate seeding densities, ECM composition (Matrigel®, BME2rgf, collagen I) and biomechanical (perfusion vs static) conditions. We then exposed the cells to a series of anti-cancer drugs (paclitaxel, olaparib, cisplatin) and compared their responses to those in 2D cultures. Finally, we generated cisplatin dose responses in 3D cultures of breast cancer cells derived from 2 PDX models. RESULTS: The microfluidic platform allows the simultaneous culture of 96 perfused micro tissues, using limited amounts of material, enabling drug screening of patient-derived material. 3D cell culture viability is improved by constant perfusion of the medium. Furthermore, the drug response of these triple negative breast cancer cells was attenuated by culture in 3D and differed from that observed in 2D substrates. CONCLUSIONS: We have investigated the use of a high-throughput organ-on-a-chip platform to select therapies. Our results have raised the possibility to use this technology in personalized medicine to support selection of appropriate drugs and to predict response to therapy in a real time fashion.
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3D-cultured breast tumor chips can be used to predict antitumor drug responses.
“Therefore, researchers propose that 3D-cultured breast tumor chips can be used to predict antitumor drug responses211,212.”
From Tumor-on-a-chip: from bioinspired design to biomedical application (2021) · cites this paper as [211]
The drug response of breast tumor cells is weakened in 3D culture compared with 2D culture.
“The researchers compared the effects of several antitumor drugs, such as paclitaxel, olaparib, and cisplatin, in 2D- and 3D-cultured breast tumor cells and found that the drug response was weakened in 3D-cultured tumor cells.”
From Tumor-on-a-chip: from bioinspired design to biomedical application (2021) · cites this paper as [211]
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Modelling cancer in microfluidic human organs-on-chips
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“A mix of Matrigel and collagen I (1:1) was used as the loading matrix.”
BackgroundInfluential
- Authors
- Lanz, H. L., Saleh, A., Kramer, B., Cairns, J., Ng, C. P., Yu, J., Trietsch, S. J., Hankemeier, T., Joore, J., Vulto, P., Weinshilboum, R., & Wang, L.
- Affiliations
- National Institutes of Health (US)
- Mimetas (Netherlands) (NL)
- Mayo Clinic (US)
- Leiden University (NL)
- ORCID
- Venue
- BMC Cancer
- Published
- 2017-11-02
- Volume
- 17
- Issue
- 1
- Pages
- 709-709
- ISSN
- 1471-2407 (ISSN-L)
- PMC
- PMC5668957
- OpenAlex
- W2765957053
- Cited by
- 135
- References
- 54
- Citations by year
- 2026: 11 · 2025: 9 · 2024: 17 · 2023: 13 · 2022: 16 · 2021: 17 · 2020: 18 · 2019: 19 · 2018: 15
- FWCI
- 6.40
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- BMC Cancer (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Leiden Repository (Leiden University) (submittedVersion, other-oa)
- Leiden Repository (Leiden University) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- National Institutes of Health (RO1 CA196640, U19 GM61388)
- Mayo Clinic (Center for Individualized Medicine Pharmacogenomics Translational Program)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Keywords
- breast cancer, triple-negative breast cancer, organ-on-a-chip, extracellular matrix, 3D cell culture, drug response prediction, treatment selection, cisplatin, paclitaxel, olaparib, patient-derived xenografts, personalized medicine, MDA-MB-453, MDA-MB-231 cells, HCC1937, BRCA1, p53, Matrigel, type I collagen, perfusion
- MeSH terms
- Antineoplastic Agents, Cell Survival, Cisplatin, Collagen, Drug Combinations, Extracellular Matrix, Female, Humans, Laminin, Mutation, Phthalazines, Piperazines, Prognosis, Proteoglycans, Tumor Suppressor Protein p53, Outcome Assessment, Health Care, Paclitaxel, Cell Culture Techniques, BRCA1 Protein, Microfluidics, Cell Line, Tumor, Triple Negative Breast Neoplasms
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