Gene expression perturbation in vitro—A growing case for three-dimensional (3D) culture systems
Abstract
Cells grown in vitro are dramatically perturbed by their new microenvironment. Analyses of genome-wide gene expression levels offer a first glance at which genes and pathways are affected in cell lines as compared to their tissues of origins. We have summarized available gene expression data and review how cell lines adapt to in vitro environments, to what degree they express markers of their tissues of origins and discuss how cells grown in three-dimensional (3D) cultures may have more physiological interactions with neighbouring cells and extracellular matrix. We will also discuss the interplay between malignant cells and stroma present in tumours but lacking in cell lines and how these differences might affect gene expression comparisons of cell lines to tumours. A model simulating impact of stromal cells on gene expression profiles is presented. Understanding the transcriptomes of cells grown in 2D and 3D cultures and how they compare to those of in vivo cells are important for improving cell line model systems and for the reconstituting of tissues in vitro.
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2D cell culture tests sometimes provide misleading and nonpredictive data for in vivo responses.
“As a result, 2D cell culture tests sometimes provide misleading and nonpredictive data for in vivo responses. 1-3”
From Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors (2014) · cites this paper as [1]
When cells are placed back into an in vivo environment or grown in a reconstituted basement membrane resembling ECM, differences in morphology, proliferation, and gene/protein expression are largely restored.
“Although cells lose many of their native in vivo characteristics after being removed from the primary tumor and cultured in a 2D system, when the cells are placed back into an in vivo environment ( i.e. , an animal model) or grown in a reconstituted basement membrane that resembles the ECM, these differences in morphology, proliferation, and gene/ protein expression are largely restored. 1,35”
From Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors (2014) · cites this paper as [1]
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- Authors
- Birgersdotter, A., Sandberg, R., & Ernberg, I.
- Affiliations
- Karolinska Institutet (SE)
- Corresponding author
- Ernberg, Ingemar
- Venue
- Seminars in Cancer Biology
- Publisher
- Elsevier BV
- Published
- 2005-10
- Volume
- 15
- Issue
- 5
- Pages
- 405-412
- ISSN
- 1044-579X (ISSN-L)
- OpenAlex
- W2154251974
- Cited by
- 591
- References
- 50
- Citations by year
- 2026: 15 · 2025: 19 · 2024: 26 · 2023: 40 · 2022: 47 · 2021: 38 · 2020: 45 · 2019: 43 · 2018: 48 · 2017: 48 · 2016: 37 · 2015: 32 · 2014: 27 · 2013: 23 · 2012: 24
- FWCI
- 0.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Seminars in Cancer Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Swedish Foundation for International Cooperation in Research and Higher Education
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- gene expression, 3D cell culture, cell lines, in vitro microenvironment, extracellular matrix, stromal cells, tumor stroma, transcriptome, 2D vs 3D culture, cell line models, tissue reconstitution, cell-cell interactions
- MeSH terms
- Cell Adhesion, Cell Line, DNA, Humans, Neoplasm Metastasis, Neoplasms, Phenotype, Transcription, Genetic, Down-Regulation, Up-Regulation, Gene Expression Regulation, Neoplastic, Coculture Techniques, Oligonucleotide Array Sequence Analysis, Cell Line, Tumor, Cell Proliferation
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