Capturing tumor complexity in vitro: Comparative analysis of 2D and 3D tumor models for drug discovery
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Two-dimensional (2D) cell cultures growing on plastic do not recapitulate the three dimensional (3D) architecture and complexity of human tumors. More representative models are required for drug discovery and validation. Here, 2D culture and 3D mono- and stromal co-culture models of increasing complexity have been established and cross-comparisons made using three standard cell carcinoma lines: MCF7, LNCaP, NCI-H1437. Fluorescence-based growth curves, 3D image analysis, immunohistochemistry and treatment responses showed that end points differed according to cell type, stromal co-culture and culture format. The adaptable methodologies described here should guide the choice of appropriate simple and complex in vitro models.
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Conventional 2D cell monolayers and 3D cell culture models are unable to recapitulate the complex biochemical and biophysical factors of the tumor microenvironment in vivo because they lack the systemic nature of tumors, leading to weak predictive ability.
“2D cell monolayers and three-dimensional cell culture models have been widely employed as initial screening models to provide a cost-efficient and simplified method to elucidate the mechanism of cancer biology or identify the efficacy and safety of a drug candidate14–16; however, they are unable to recapitulate complex biochemical and biophysical factors of the tumor microenvironment (TME) in vivo”
From Tumor-on-a-chip: from bioinspired design to biomedical application (2021) · cites this paper as [24]
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- Authors
- Stock, K., Estrada, M. F., Vidic, S., Gjerde, K., Rudisch, A., Santo, V. E., Barbier, M., Blom, S., Arundkar, S. C., Selvam, I., Osswald, A., Stein, Y., Gruenewald, S., Brito, C., van Weerden, W., Rotter, V., Boghaert, E., Oren, M., Sommergruber, W., Chong, Y., de Hoogt, R., & Graeser, R.
- Affiliations
- Bayer (Germany) (DE)
- Instituto de Biologia Experimental e Tecnológica (PT)
- University of Primorska (SI)
- Janssen (Belgium) (BE)
- Boehringer Ingelheim (Austria) (AT)
- University of Helsinki (FI)
- Weizmann Institute of Science (IL)
- AbbVie (United States) (US)
- Boehringer Ingelheim (Germany) (DE)
- Corresponding author
- Graeser, Ralph
- ORCID
- Venue
- Scientific Reports
- Published
- 2016-07-01
- Volume
- 6
- Issue
- 1
- Pages
- 28951-28951
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4929472
- OpenAlex
- W2471907651
- Cited by
- 253
- References
- 52
- Citations by year
- 2026: 15 · 2025: 20 · 2024: 20 · 2023: 31 · 2022: 25 · 2021: 38 · 2020: 39 · 2019: 29 · 2018: 20 · 2017: 15 · 2016: 1
- FWCI
- 10.43
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Työväentutkimus Vuosikirja (submittedVersion, other-oa)
- Funders
- European Federation of Pharmaceutical Industries and Associations
- Innovative Medicines Initiative (115188)
- Fundação para a Ciência e a Tecnologia (EXPL/BBB-IMG/0363/2013, SFRH/BD/52208/2013)
- 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
- 3D tumor models, 2D cell culture, in vitro tumor model, drug discovery, breast cancer, prostate cancer, lung cancer, MCF-7 cells, LNCaP cells, model comparison, tumor growth curves, 3D image analysis
- MeSH terms
- Humans, Stromal Cells, Spheroids, Cellular, Coculture Techniques, Imaging, Three-Dimensional, Cell Line, Tumor, MCF-7 Cells
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