The DOI matches its Crossref record; 27 of the 28 references it cites were found in a registry or an index.
Three-dimensional culture of melanoma cells profoundly affects gene expression profile: A high density oligonucleotide array study
Abstract
Growth in three-dimensional (3D) architectures has been suggested to play an important role in tumor expansion and in the resistance of cancers to treatment with drugs or cytokines or irradiation. To obtain an insight into underlying molecular mechanisms, we addressed gene expression profiles of NA8 melanoma cells cultured in bidimensional monolayers (2D) or in 3D multicellular tumor spheroids (MCTS). MCTS containing 10-30,000 cells were generated upon overnight culture in poly-Hydroxyethylmethacrylate (polyHEMA) coated plates. Kinetics of cell proliferation in MCTS was significantly slower than in monolayer cultures. Following long-term culture (>10 days), however, MCTS showed highly compact and organised cell growth in outer layers, with necrotic cores. Oligonucleotide microarray analysis of the expression of over 20,000 genes was performed on cells cultured in standard 2D, in the presence of collagen as model of extracellular matrix (ECM), or in MCTS. Gene expression profiles of cells cultured in 2D in the presence or absence of ECM were highly similar, with >/=threefold differences limited to five genes. In contrast, culture in MCTS resulted in the significant, >/=threefold, upregulation of the expression of >100 transcripts while 73 were >/=threefold downregulated. In particular, genes encoding CXCL1, 2, and 3 (GRO-alpha, -beta, and gamma), IL-8, CCL20 (MIP-3alpha), and Angiopoietin-like 4 were significantly upregulated, whereas basic FGF and CD49d encoding genes were significantly downregulated. Oligonucleotide chip data were validated at the gene and protein level by quantitative real-time PCR, ELISA, and cell surface staining assays. Taken together, our data indicate that structural modifications of the architecture of tumor cell cultures result in a significant upregulation of the expression of a number of genes previously shown to play a role in melanoma progression and metastatic process.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“transcriptomic analysis of melanoma cells cultured as monolayers, monolayers with ECM, and spheroids revealed that gene expression remained largely unchanged between the two monolayer conditions, while spheroid cultures exhibited substantial differences [194,195].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [194]
In the citing paper
“Over 100 transcripts were found to be upregulated and approximately 70 downregulated, with many of the altered genes associated with tumor progression and metastatic behavior [194].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [194]
In the citing paper
“gene expression patterns in spheroids more closely resemble those found in solid tumors than in monolayer cultures [112,193,194].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [194]
Citations
Cites
Role of cell shape in growth control
Folkman, J., & Moscona, A. (1978) · Nature · doi:10.1038/273345a0 · Cited by 2,422
Interleukin-8 as a macrophage-derived mediator of angiogenesis
Koch, A. E., Polverini, P. J., Kunkel, S. L., Harlow, L. A., DiPietro, L. A., Elner, V. M., Elner, S. G., & Strieter, R. M. (1992) · Science · doi:10.1126/science.1281554 · Cited by 2,135
Cell and environment interactions in tumor microregions: the multicell spheroid model.
Sutherland, R. M. (1988) · Science · doi:10.1126/science.2451290 · Cited by 1,803
Cell adhesion and signalling by cadherins and Ig-CAMs in cancer
Cavallaro, U., & Christofori, G. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1276 · Cited by 1,314
Kelm, J. M., Timmins, N. E., Brown, C. J., Fussenegger, M., & Nielsen, L. K. (2003) · Biotechnology and Bioengineering · doi:10.1002/bit.10655 · Cited by 934
Weaver, V. M., Lelièvre, S. A., Lakins, J. N., Chrenek, M. A., Jones, J., Giancotti, F. G., Werb, Z., & Bissell, M. J. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00125-3 · Cited by 794
A listing of human tumor antigens recognized by T cells
Renkvist, N., Castelli, C., Robbins, P. F., & Parmiani, G. (2001) · Cancer Immunology Immunotherapy · doi:10.1007/s002620000169 · Cited by 694
Comparison of alamar blue and MTT assays for high through-put screening
Hamid, R., Rotshteyn, Y., Rabadi, L., Parikh, R., & Bullock, P. L. (2004) · Toxicology in Vitro · doi:10.1016/j.tiv.2004.03.012 · Cited by 572
Roles of tumour localization, second signals and cross priming in cytotoxic T-cell induction
Ochsenbein, A. F., Sierro, S. R., Odermatt, B., Pericin, M., Karrer, U., Hermans, J., Hemmi, S., Hengartner, H., & Zinkernagel, R. M. (2001) · Nature · doi:10.1038/35082583 · Cited by 495
Multicellular resistance: a paradigm for clinical resistance?
Desoize, B. (2000) · Critical Reviews in Oncology/Hematology · doi:10.1016/s1040-8428(00)00086-x · Cited by 399
Cited by
Sorted by citations
The third dimension bridges the gap between cell culture and live tissue
Pampaloni, F., Reynaud, E. G., & Stelzer, E. H. K. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2236 · Cited by 2,817
2D and 3D Cell Cultures - a Comparison of Different Types of Cancer Cell Cultures
Kapałczyńska, M., Kolenda, T., Przybyła, W., Zajączkowska, M., Teresiak, A., Filas, V., Ibbs, M., Bliźniak, R., Łuczewski, Ł., & Lamperska, K. (2016) · Archives of Medical Science · doi:10.5114/aoms.2016.63743 · Cited by 1,499
Vinci, M., Gowan, S., Boxall, F., Patterson, L., Zimmermann, M., Court, W., Lomas, C., Mendiola, M., Hardisson, D., & Eccles, S. A. (2012) · BMC Biology · doi:10.1186/1741-7007-10-29 · Cited by 1,024
3D tumor spheroids: an overview on the tools and techniques used for their analysis
Costa, E. C., Moreira, A. F., de Melo-Diogo, D., Gaspar, V. M., Carvalho, M. P., & Correia, I. J. (2016) · Biotechnology Advances · doi:10.1016/j.biotechadv.2016.11.002 · Cited by 929
Single-cell RNA-seq: advances and future challenges
Saliba, A.-E., Westermann, A. J., Gorski, S. A., & Vogel, J. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku555 · Cited by 847
Metadata
- Authors
- Ghosh, S., Spagnoli, G. C., Martin, I., Ploegert, S., Demougin, P., Heberer, M., & Reschner, A.
- Affiliations
- University of Basel (CH)
- Corresponding author
- Reschner, Anca
- Venue
- Journal of Cellular Physiology
- Publisher
- Wiley
- Published
- 2005-03-02
- Volume
- 204
- Issue
- 2
- Pages
- 522-531
- ISSN
- 0021-9541 (ISSN-L)
- 1097-4652
- OpenAlex
- W2015893533
- Cited by
- 326
- References
- 28
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 15 · 2023: 19 · 2022: 16 · 2021: 23 · 2020: 24 · 2019: 18 · 2018: 12 · 2017: 20 · 2016: 30 · 2015: 13 · 2014: 19 · 2013: 21 · 2012: 15
- FWCI
- 5.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cellular Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Swiss Bridge Foundation
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
- Keywords
- melanoma, 3D cell culture, tumor spheroids, gene expression profiles, extracellular matrix, collagen, tumor architecture, CXCL chemokines, interleukin-8, CCL20, ANGPTL4, basic FGF, CD49d, tumor necrosis, metastasis
- MeSH terms
- Cell Division, Enzyme-Linked Immunosorbent Assay, Humans, Melanoma, Staining and Labeling, Tumor Cells, Cultured, Down-Regulation, Up-Regulation, Polymerase Chain Reaction, Spheroids, Cellular, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
