The molecular portrait of in vitro growth by meta-analysis of gene-expression profiles
Open accessAbstract
Background: Cell lines as model systems of tumors and tissues are essential in molecular biology, although they only approximate the properties of in vivo cells in tissues. Cell lines have been selected under in vitro conditions for a long period of time, affecting many specific cellular pathways and processes. Results: To identify the transcriptional changes caused by long term in vitro selection, we performed a gene-expression meta-analysis and compared 60 tumor cell lines (of nine tissue origins) to 135 human tissue and 176 tumor tissue samples. Using significance analysis of microarrays we demonstrated that cell lines showed statistically significant differential expression of approximately 30% of the approximately 7,000 genes investigated compared to the tissues. Most of the differences were associated with the higher proliferation rate and the disrupted tissue organization in vitro. Thus, genes involved in cell-cycle progression, macromolecule processing and turnover, and energy metabolism were upregulated in cell lines, whereas cell adhesion molecules and membrane signaling proteins were downregulated. Conclusion: Detailed molecular understanding of how cells adapt to the in vitro environment is important, as it will both increase our understanding of tissue organization and result in a refined molecular portrait of proliferation. It will further indicate when to use immortalized cell lines, or when it is necessary to instead use three-dimensional cultures, primary cell cultures or tissue biopsies.
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Genes associated with metabolism and macromolecular turnover were upregulated in monolayers, while those involved in adhesion and membrane signaling were downregulated.
“Genes associated with metabolism and macromolecular turnover were upregulated in monolayers, while those involved in adhesion and membrane signaling were downregulated [176].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [176]
The Results section reports that genes involved in energy metabolism and macromolecular processing and degradation were upregulated in cell lines, while adhesion and signaling genes were downregulated. The study compared long-term cultured cell lines with tissues and tumors; it does not specifically establish these findings for monolayers. (LLM, conf=0.82)
Experimental — accuracy not yet measuredIn a meta-analysis involving NCI-60 monolayers and clinical tumor samples, approximately 30% of ~7000 genes showed altered expression.
“In a meta-analysis involving NCI-60 monolayers and clinical tumor samples, approximately 30% of ~7000 genes showed altered expression [176].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [176]
The Background reports that the meta-analysis compared NCI-60 cell lines with human normal and tumor tissues and found differential expression in approximately 30% of roughly 7,000 genes. The Materials and methods identifies the NCI-60 data, but our copy does not establish that the cell lines were grown as monolayers; that culture-specific description is unsupported. (LLM, conf=0.86)
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“Gene expression studies comparing monolayer cultures to tumor tissues have demonstrated significant differences [176].”
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- Authors
- Sandberg, R., & Ernberg, I.
- Affiliations
- Karolinska Institutet (SE)
- Corresponding author
- Sandberg, Rickard
- Venue
- Genome Biology
- Published
- 2005-07-27
- Volume
- 6
- Issue
- 8
- Pages
- R65-R65
- ISSN
- 1465-6906 (ISSN-L)
- 1474-760X
- PMC
- PMC1273632
- OpenAlex
- W2150864430
- Cited by
- 84
- References
- 40
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 1 · 2023: 1 · 2022: 4 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 5 · 2017: 5 · 2016: 8 · 2015: 4 · 2014: 2 · 2013: 3 · 2012: 9
- FWCI
- 0.35
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Genome biology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cancerfonden
- Vetenskapsrådet
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- cancer cell lines, in vitro selection, gene expression profiling, meta-analysis, cell proliferation, adhesion molecules, cell cycle progression, energy metabolism, tissue organization, immortalized cell lines, 3D cell culture, primary cell culture
- MeSH terms
- Cell Adhesion, Cell Division, Cell Line, Humans, Transcription, Genetic, Reproducibility of Results, Down-Regulation, Up-Regulation, Gene Expression Profiling, Cell Line, Tumor
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