Modeling dynamic reciprocity: Engineering three-dimensional culture models of breast architecture, function, and neoplastic transformation
Open accessAbstract
In order to understand why cancer develops as well as predict the outcome of pharmacological treatments, we need to model the structure and function of organs in culture so that our experimental manipulations occur under physiological contexts. This review traces the history of the development of a prototypic example, the three-dimensional (3D) model of the mammary gland acinus. We briefly describe the considerable information available on both normal mammary gland function and breast cancer generated by the current model and present future challenges that will require an increase in its complexity. We propose the need for engineered tissues that faithfully recapitulate their native structures to allow a greater understanding of tissue function, dysfunction, and potential therapeutic intervention.
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Cells in a 3D culture environment differ in gene, protein, and cell receptor expression from 2D-cultured cells.
“In addition to the previously mentioned differences in physical and physiological properties, researchers have also found that cells in a 3D culture environment differ in gene, protein, and cell receptor expression from 2D-cultured cells. 8-10”
From Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors (2014) · cites this paper as [10]
Section 3.1 reports that the extracellular matrix alters gene expression in mammary epithelial cells, and section 3.2 describes protein-expression differences revealed by 3D culture compared with 2D culture. Section 4.1 says matrix components alter estrogen-receptor expression, but does not establish a direct 3D-versus-2D comparison of receptor expression. The evidence is also specific to mammary epithelial models rather than cells generally; page numbers are unavailable in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredCells cultured in three-dimensional arrangements exhibit notable differences in morphology and physiology compared to cells grown in monolayers.
“cells cultured in three-dimensional arrangements exhibit notable differences in morphology and physiology compared to cells grown in monolayers [188,189,190].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [189]
Cells in the 3D culture environment differ morphologically and physiologically from cells in the 2D culture environment.
“In fact, research has found that cells in the 3D culture environment differ morphologically and physiologically from cells in the 2D culture environment. 8-10”
From Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors (2014) · cites this paper as [10]
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References 140 · Cited by 332
- Authors
- Nelson, C. M., & Bissell, M. J.
- Affiliations
- Lawrence Berkeley National Laboratory (US)
- Corresponding author
- Bissell, Mina J.
- Venue
- Seminars in Cancer Biology
- Publisher
- Elsevier BV
- Published
- 2005-10
- Volume
- 15
- Issue
- 5
- Pages
- 342-352
- ISSN
- 1044-579X (ISSN-L)
- PMC
- PMC2933210
- OpenAlex
- W2018494545
- Cited by
- 332
- References
- 140
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 7 · 2023: 9 · 2022: 9 · 2021: 10 · 2020: 19 · 2019: 17 · 2018: 16 · 2017: 9 · 2016: 25 · 2015: 19 · 2014: 22 · 2013: 29 · 2012: 16
- FWCI
- 1.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Seminars in Cancer Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (CA-57621, CA-64786, R37CA064786, R01CA057621, R01CA064786)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- three-dimensional culture model, breast cancer, mammary gland development, tissue engineering, organotypic culture, oncogenic transformation
- MeSH terms
- Animals, Breast Neoplasms, Cell Transformation, Neoplastic, Humans, Mammary Glands, Animal, Models, Anatomic, Models, Biological, Phenotype, Tissue Engineering, Mammary Glands, Human
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