The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Impact of the 3D Microenvironment on Phenotype, Gene Expression, and EGFR Inhibition of Colorectal Cancer Cell Lines
Open accessAbstract
Three-dimensional (3D) tumor cell cultures grown in laminin-rich-extracellular matrix (lrECM) are considered to reflect human tumors more realistic as compared to cells grown as monolayer on plastic. Here, we systematically investigated the impact of ECM on phenotype, gene expression, EGFR signaling pathway, and on EGFR inhibition in commonly used colorectal cancer (CRC) cell lines. LrECM on-top (3D) culture assays were performed with the CRC cell lines SW-480, HT-29, DLD-1, LOVO, CACO-2, COLO-205 and COLO-206F. Morphology of lrECM cultivated CRC cell lines was determined by phase contrast and confocal laser scanning fluorescence microscopy. Proliferation of cells was examined by MTT assay, invasive capacity of the cell lines was assayed using Matrigel-coated Boyden chambers, and migratory activity was determined employing the Fence assay. Differential gene expression was analyzed at the transcriptional level by the Agilent array platform. EGFR was inhibited by using the specific small molecule inhibitor AG1478. A specific spheroid growth pattern was observed for all investigated CRC cell lines. DLD-1, HT-29 and SW-480 and CACO-2 exhibited a clear solid tumor cell formation, while LOVO, COLO-205 and COLO-206F were characterized by forming grape-like structures. Although the occurrence of a spheroid morphology did not correlate with an altered migratory, invasive, or proliferative capacity of CRC cell lines, gene expression was clearly altered in cells grown on lrECM as compared to 2D cultures. Interestingly, in KRAS wild-type cell lines, inhibition of EGFR was less effective in lrECM (3D) cultures as compared to 2D cell cultures. Thus, comparing both 2D and 3D cell culture models, our data support the influence of the ECM on cancer growth. Compared to conventional 2D cell culture, the lrECM (3D) cell culture model offers the opportunity to investigate permanent CRC cell lines under more physiological conditions, i.e. in the context of molecular therapeutic targets and their pharmacological inhibition.
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“The proliferation rates of cells cultured in 3D and 2D are usually different, and are cell line and matrix dependent.”
From Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors (2014) · cites this paper as [29]
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“Overall, the morphological appearance of 3D spheroids is primarily cell line dependent. 29,35,37”
From Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors (2014) · cites this paper as [29]
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“A variety of cell lines showed reduced proliferation rate in 3D cultures compared to those cultured in 2D. 17,27-31”
From Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors (2014) · cites this paper as [29]
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“A similar trend was observed in hepatocellular carcinoma models, where monolayers showed enrichment in structural gene expression, whereas spheroids upregulated genes related to metabolism and biosynthesis [196,197,198].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [197]
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Metadata
- Authors
- Luca, A. C., Mersch, S., Deenen, R., Schmidt, S., Messner, I., Schäfer, K.-L., Baldus, S. E., Huckenbeck, W., Piekorz, R. P., Knoefel, W. T., Krieg, A., & Stoecklein, N. H.
- Affiliations
- Düsseldorf University Hospital (DE)
- Heinrich Heine University Düsseldorf (DE)
- Corresponding author
- Krieg, Andreas
- Stoecklein, Nikolas H.
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-03-26
- Volume
- 8
- Issue
- 3
- Pages
- e59689
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3608563
- OpenAlex
- W1983051794
- Cited by
- 341
- References
- 31
- Citations by year
- 2026: 11 · 2025: 14 · 2024: 18 · 2023: 29 · 2022: 27 · 2021: 39 · 2020: 40 · 2019: 29 · 2018: 25 · 2017: 33 · 2016: 29 · 2015: 18 · 2014: 25 · 2013: 4
- FWCI
- 13.56
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Univ. Duesseldorf: Duesseldorfer Dokumenten- und Publikationsserver (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- Deutsche Forschungsgemeinschaft (SFB728)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- colorectal cancer, 3D cell culture, tumor microenvironment, EGFR signaling, EGFR inhibition, AG1478, gene expression, cell morphology, spheroid formation, cell invasion, cell migration, KRAS wild-type, 2D vs 3D culture comparison, colorectal cancer cell lines
- MeSH terms
- Extracellular Matrix, Humans, Laminin, Phenotype, Colorectal Neoplasms, Gene Expression Regulation, Neoplastic, Spheroids, Cellular, Cell Culture Techniques, Cell Line, Tumor, Protein Kinase Inhibitors, Cell Proliferation, Tumor Microenvironment, ErbB Receptors
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