Assessment of different 3D culture systems to study tumor phenotype and chemosensitivity in pancreatic ductal adenocarcinoma
Open accessAbstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease with a very poor prognosis, due to the influence of the tumor stroma, which promotes tumor growth, early invasion and chemoradiation resistance. Efforts to develop models for identifying novel anticancer therapeutic compounds have been hampered by the limited ability of in vitro models to mimic these in vivo tumor-stroma interactions. This has led to the development of various three-dimensional (3D) culture platforms recapitulating the in vivo tumor-stroma crosstalk and designed to better understand basic cancer processes and screen drug action. However, a consensus for different experimental 3D platforms is still missing in PDAC. We compared four PDAC cell lines of different malignancy grown in 2D monolayers to three of the more commonly used 3D techniques (ultralow adhesion concave microwells, Matrigel inclusion and organotypic systems) and to tumors derived from their orthotopic implantation in mice. In these 3D platforms, we observed that cells grow with very different tumor morphologies and the organotypic setting most closely resembles the tumor cytoarchitecture obtained by orthotopically implanting the four cell lines in mice. We then analyzed the molecular and cellular responses of one of these cell lines to epidermal growth factor receptor (EGFR) stimulation with EGF and inhibition with erlotinib and found that only in the 3D platforms, and especially the organotypic, cells: i) responded to EGF by changing the expression of signalling components underlying cell-stroma crosstalk and tissue architecture, growth, invasion and drug resistance (E-cadherin, EGFR, ezrin, β1 integrin, NHERF1 and HIF-1α) similar to those reported in vivo; ii) had stimulated growth and increased erlotinib sensitivity in response to EGF, more faithfully mimicking their known in vivo behaviour. Altogether, these results, indicate the organotypic as the most relevant physiological 3D system to study the complex tumor stroma interactions driving progression and determining chemio-resistance.
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Ex vivo 3D models of tumor growth are being increasingly adopted, as a number of comparative studies between 3D spheroids and 2D monolayer cultures have shown that 3D culture more faithfully recapitulates in vivo biology.
“Ex vivo 3D models of tumor growth are being increasingly adopted, as a number of comparative studies between 3D spheroids and 2D monolayer cultures have shown that 3D culture more faithfully recapitulates in vivo biology38–40.”
From Occult polyclonality of preclinical pancreatic cancer models drives in vitro evolution (2022) · cites this paper as [38]
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- Authors
- ZEEBERG, K., CARDONE, R. A., GRECO, M. R., SACCOMANO, M., NØHR-NIELSEN, A., ALVES, F., PEDERSEN, S. F., & RESHKIN, S. J.
- Affiliations
- University of Bari Aldo Moro (IT)
- Max Planck Institute of Experimental Medicine (DE)
- University of Copenhagen (DK)
- ORCID
- Venue
- International Journal of Oncology
- Publisher
- Spandidos Publications
- Published
- 2016-05-10
- Volume
- 49
- Issue
- 1
- Pages
- 243-252
- ISSN
- 1019-6439 (ISSN-L)
- 1791-2423
- OpenAlex
- W2373958043
- Cited by
- 33
- References
- 40
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 8 · 2021: 9 · 2020: 3 · 2019: 3 · 2018: 2
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- International Journal of Oncology (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Digital Library (submittedVersion)
- GRO (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion, cc-by-nc-nd)
- Funders
- Associazione Italiana per la Ricerca sul Cancro (11348)
- FP7 People: Marie-Curie Actions (FP7-PEOPLE-2011-ITN, 289648)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- pancreatic ductal adenocarcinoma, 3D culture system, tumor stroma, tumor-stroma interactions, organotypic culture, orthotopic mouse model, chemosensitivity, erlotinib, EGFR signaling, epidermal growth factor, drug resistance, tumor morphology, NHERF1, HIF-1α, beta1 integrin, E-cadherin, ezrin
- MeSH terms
- Erlotinib Hydrochloride, Adenocarcinoma, Animals, Epidermal Growth Factor, Humans, Stromal Cells, Cell Culture Techniques, Drug Resistance, Neoplasm, Carcinoma, Pancreatic Ductal, Cell Line, Tumor, Cell Proliferation, Mice, ErbB Receptors
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 ›
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