Alteration of Cellular Behavior and Response to PI3K Pathway Inhibition by Culture in 3D Collagen Gels
Open accessAbstract
Most investigations into cancer cell drug response are performed with cells cultured on flat (2D) tissue culture plastic. Emerging research has shown that the presence of a three-dimensional (3D) extracellular matrix (ECM) is critical for normal cell behavior including migration, adhesion, signaling, proliferation and apoptosis. In this study we investigate differences between cancer cell signaling in 2D culture and a 3D ECM, employing real-time, live cell tracking to directly observe U2OS human osteosarcoma and MCF7 human breast cancer cells embedded in type 1 collagen gels. The activation of the important PI3K signaling pathway under these different growth conditions is studied, and the response to inhibition of both PI3K and mTOR with PI103 investigated. Cells grown in 3D gels show reduced proliferation and migration as well as reduced PI3K pathway activation when compared to cells grown in 2D. Our results quantitatively demonstrate that a collagen ECM can protect U2OS cells from PI103. Overall, our data suggests that 3D gels may provide a better medium for investigation of anti-cancer drugs than 2D monolayers, therefore allowing better understanding of cellular response and behavior in native like environments.
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Proliferation rates of cells cultured in 3D and 2D are usually different and are cell line and matrix dependent.
“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 [28]
A variety of cell lines showed reduced proliferation rate in 3D cultures compared to those cultured in 2D.
“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 [28]
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References 61 · Cited by 84
- Authors
- Fallica, B., Maffei, J. S., Villa, S., Makin, G., & Zaman, M.
- Affiliations
- Boston University (US)
- Manchester Academic Health Science Centre (GB)
- Corresponding author
- Zaman, Muhammad
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-10-23
- Volume
- 7
- Issue
- 10
- Pages
- e48024
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3479126
- OpenAlex
- W2090722243
- Cited by
- 84
- References
- 61
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 2 · 2023: 8 · 2022: 4 · 2021: 7 · 2020: 8 · 2019: 7 · 2018: 7 · 2017: 6 · 2016: 8 · 2015: 6 · 2014: 12 · 2013: 4
- FWCI
- 3.33
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion, cc-by)
- Funders
- Consortia for Improving Medicine with Innovation and Technology
- Research Councils UK
- Engineering and Physical Sciences Research Council (EP/G041733/1)
- National Institute of General Medical Sciences (T32GM008541)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- 3D collagen gel, extracellular matrix, PI3K signaling, mTOR inhibition, drug resistance, U2OS osteosarcoma cells, MCF-7 cells, cell proliferation, cell migration, live cell tracking, 2D vs 3D culture
- MeSH terms
- Cell Adhesion, Cell Movement, Extracellular Matrix, Furans, Gels, Humans, Neoplasms, Pyridines, Pyrimidines, Blotting, Western, Signal Transduction, Apoptosis, Microscopy, Confocal, Microscopy, Video, Cell Culture Techniques, Phosphatidylinositol 3-Kinases, Collagen Type I, Cell Line, Tumor, Cell Proliferation, TOR Serine-Threonine Kinases, MCF-7 Cells
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