Three-Dimensional In Vitro Co-Culture Model of Breast Tumor using Magnetic Levitation
Open accessAbstract
In this study, we investigate a novel in vitro model to mimic heterogeneous breast tumors without the use of a scaffold while allowing for cell-cell and tumor-fibroblast interactions. Previous studies have shown that magnetic levitation system under conventional culturing conditions results in the formation of three-dimensional (3D) structures, closely resembling in vivo tissues (fat tissue, vasculature, etc.). Three-dimensional heterogeneous tumor models for breast cancer were designed to effectively model the influences of the tumor microenvironment on drug efficiency. Various breast cancer cells were co-cultured with fibroblasts and then magnetically levitated. Size and cell density of the resulting tumors were measured. The model was phenotypically compared to in vivo tumors and examined for the presence of ECM proteins. Lastly, the effects of tumor stroma in the 3D in vitro model on drug transport and efficiency were assessed. Our data suggest that the proposed 3D in vitro breast tumor is advantageous due to the ability to: (1) form large-sized (millimeter in diameter) breast tumor models within 24 h; (2) control tumor cell composition and density; (3) accurately mimic the in vivo tumor microenvironment; and (4) test drug efficiency in an in vitro model that is comparable to in vivo tumors.
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In breast tumor models, spheroids with higher fibroblast content exhibited decreased diffusion of dextran dye and diminished cytotoxicity following doxorubicin exposure.
“In breast tumor models, spheroids generated with higher fibroblast content exhibited decreased diffusion of dextran dye and diminished cytotoxicity following doxorubicin exposure [208].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [208]
The Results (page not provided) report about 10% greater dextran penetration in tumors with 30% fibroblasts than in those with 70% fibroblasts. The doxorubicin Results and Discussion compare drug effects across 2D and 3D cultures and between doxorubicin and Doxil, but do not show diminished doxorubicin cytotoxicity specifically as fibroblast content increases. (LLM, conf=0.88)
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- Authors
- Jaganathan, H., Gage, J., Leonard, F., Srinivasan, S., Souza, G. R., Dave, B., & Godin, B.
- Affiliations
- Houston Methodist (US)
- Nano3D Biosciences (United States) (US)
- Corresponding author
- Godin, Biana
- Venue
- Scientific Reports
- Published
- 2014-10-01
- Volume
- 4
- Issue
- 1
- Pages
- 6468-6468
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4180823
- OpenAlex
- W2041636145
- Cited by
- 231
- References
- 34
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 24 · 2023: 15 · 2022: 11 · 2021: 22 · 2020: 28 · 2019: 32 · 2018: 31 · 2017: 25 · 2016: 20 · 2015: 8 · 2014: 1
- FWCI
- 9.34
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Scientific Reports (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (U54CA151668, U54CA143837)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- breast cancer, 3D tumor models, magnetic levitation, co-culture, tumor microenvironment, tumor stroma, extracellular matrix, drug transport, drug efficacy testing, scaffold-free culture
- MeSH terms
- Antineoplastic Agents, Breast Neoplasms, Cells, Cultured, Extracellular Matrix, Female, Fibroblasts, Humans, Lung, Stromal Cells, Spheroids, Cellular, Coculture Techniques, Tumor Microenvironment, Magnetic Phenomena, In Vitro Techniques
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