Halfway between 2D and Animal Models: Are 3D Cultures the Ideal Tool to Study Cancer-Microenvironment Interactions?
Open accessAbstract
An area that has come to be of tremendous interest in tumor research in the last decade is the role of the microenvironment in the biology of neoplastic diseases. The tumor microenvironment (TME) comprises various cells that are collectively important for normal tissue homeostasis as well as tumor progression or regression. Seminal studies have demonstrated the role of the dialogue between cancer cells (at many sites) and the cellular component of the microenvironment in tumor progression, metastasis, and resistance to treatment. Using an appropriate system of microenvironment and tumor culture is the first step towards a better understanding of the complex interaction between cancer cells and their surroundings. Three-dimensional (3D) models have been widely described recently. However, while it is claimed that they can bridge the gap between in vitro and in vivo, it is sometimes hard to decipher their advantage or limitation compared to classical two-dimensional (2D) cultures, especially given the broad number of techniques used. We present here a comprehensive review of the different 3D methods developed recently, and, secondly, we discuss the pros and cons of 3D culture compared to 2D when studying interactions between cancer cells and their microenvironment.
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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 [21]
Obtaining concordance between animal models and clinical trials remains challenging, with an average rate of concordant results that barely reaches 8%.
“Seymour and Ghert et al. demonstrated that obtaining concordance between animal models and clinical trials remains challenging, with an average rate of concordant results that barely reaches 8%21,39,40.”
From Tumor-on-a-chip: from bioinspired design to biomedical application (2021) · cites this paper as [21]
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- [109]El-Gewely M.R. Biotechnology Annual Review Elsevier Amsterdam, The Netherlands 2008 Volume 14 1 475
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Tumor-on-a-chip: from bioinspired design to biomedical application
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- Authors
- Hoarau-Véchot, J., Rafii, A., Touboul, C., & Pasquier, J.
- Affiliations
- Weill Cornell Medical College in Qatar (QA)
- Inserm (FR)
- Corresponding author
- Pasquier, Jennifer
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2018-01-18
- Volume
- 19
- Issue
- 1
- Pages
- 181
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC5796130
- OpenAlex
- W2788914936
- Cited by
- 489
- References
- 159
- Citations by year
- 2026: 35 · 2025: 46 · 2024: 47 · 2023: 85 · 2022: 74 · 2021: 76 · 2020: 74 · 2019: 42 · 2018: 10
- FWCI
- 4.11
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- 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
- tumor microenvironment, 3D cell culture, 2D cell culture, tumor progression, metastasis, treatment resistance, in vitro model, animal models
- MeSH terms
- Animals, Cell Movement, Models, Biological, Spheroids, Cellular, Cell Culture Techniques, Hydrogels, Microfluidics, Cell Proliferation, Tumor Microenvironment, Bioprinting
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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