The morphologies of breast cancer cell lines in three‐dimensional assays correlate with their profiles of gene expression
Open accessAbstract
3D cell cultures are rapidly becoming the method of choice for the physiologically relevant modeling of many aspects of non‐malignant and malignant cell behavior ex vivo. Nevertheless, only a limited number of distinct cell types have been evaluated in this assay to date. Here we report the first large scale comparison of the transcriptional profiles and 3D cell culture phenotypes of a substantial panel of human breast cancer cell lines. Each cell line adopts a colony morphology of one of four main classes in 3D culture. These morphologies reflect, at least in part, the underlying gene expression profile and protein expression patterns of the cell lines, and distinct morphologies were also associated with tumor cell invasiveness and with cell lines originating from metastases. We further demonstrate that consistent differences in genes encoding signal transduction proteins emerge when even tumor cells are cultured in 3D microenvironments.
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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 [35]
The Introduction (page not provided) says that growing non-malignant mammary cells in reconstituted basement membrane can largely restore functional and morphological differentiation. The Results and Discussion (pages not provided) describe differences in proliferation and gene/protein expression between 2D and 3D cultures, but do not establish that all these features are largely restored to their in vivo state; the paper also does not demonstrate restoration by placing cells in an animal model. (LLM, conf=0.84)
Experimental — accuracy not yet measuredOverall, the morphological appearance of 3D spheroids is primarily cell line dependent.
“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 [35]
The Results (section 2.1) show that the tested breast epithelial cell lines adopt distinct morphologies in a 3D laminin-rich extracellular-matrix assay, supporting cell-line dependence in that setting. The paper does not establish that morphology is primarily cell-line dependent for 3D spheroids generally. (LLM, conf=0.83)
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References 63 · Cited by 2
Research works printed but not linked: 1
- Gazdar, A.F. , Kurvari, V. , Virmani, A. , Gollahon, L. , Sakaguchi, M. , Westerfield, M. , Kodagoda, D. , Stasny, V. , Cunningham, H.T. , Wistuba, I.I. , 1998. Characterization of paired tumor and non-tumor cell lines established from patients with breast cancer. International Journal of Cancer. 78, 766–774. [DOI] [PubMed] [Google Scholar]
- Authors
- Kenny, P. A., Lee, G. Y., Myers, C. A., Neve, R. M., Semeiks, J. R., Spellman, P. T., Lorenz, K., Lee, E. H., Barcellos-Hoff, M. H., Petersen, O. W., Gray, J. W., & Bissell, M. J.
- Affiliations
- Lawrence Berkeley National Laboratory (US)
- University of Copenhagen (DK)
- Corresponding author
- Bissell, Mina J.
- Venue
- Molecular Oncology
- Publisher
- Wiley
- Published
- 2007-03-14
- Volume
- 1
- Issue
- 1
- Pages
- 84-96
- ISSN
- 1574-7891 (ISSN-L)
- 1878-0261
- PMC
- PMC2391005
- OpenAlex
- W201784232
- Cited by
- 2
- References
- 63
- Citations by year
- 2016: 1 · 2015: 1
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Oncology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of North Texas Digital Library (University of North Texas) (submittedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Lawrence Berkeley National Laboratory
- Funders
- National Cancer Institute (U54CA126552, R01CA064786, U54CA112970)
- 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 › Mechanisms of cancer metastasis
- Keywords
- breast cancer cell lines, 3D cell culture, cell morphology, gene expression profiles, gene expression profiling, tumor invasion, metastatic cell lines, signal transduction genes, protein expression, tumor microenvironment
- MeSH terms
- Breast Neoplasms, Female, Humans, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasm Proteins, Signal Transduction, Gene Expression Regulation, Neoplastic, Cell Culture Techniques, Cell Line, Tumor
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