Cited by 341Cancer Cells and MetastasisCellular Mechanics and Interactions3D Printing in Biomedical Research

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

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Abstract

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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Crossref · 10.1371/journal.pone.0059689

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  1. PD Yurchenco, 1992, Laminin forms an independent network in basement membranes, J Cell Biol, 117, 1119

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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.
Venue
PLoS ONE
Published
2013-03-26
Volume
8
Issue
3
Pages
e59689
ISSN
1932-6203 (ISSN-L)
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
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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