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International Journal of Oncology
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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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Article

Assessment of different 3D culture systems to study tumor phenotype and chemosensitivity in pancreatic ductal adenocarcinoma

  • Authors:
    • Katrine Zeeberg
    • Rosa Angela Cardone
    • Maria Raffaella Greco
    • Mara Saccomano
    • Asbjørn Nøhr-Nielsen
    • Frauke Alves
    • Stine Falsig Pedersen
    • Stephan Joel Reshkin
  • View Affiliations / Copyright

    Affiliations: Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari, Bari, Italy, Max-Planck-Institute of Experimental Medicine, Goettingen, Germany, Section for Cell and Developmental Biology, Department of Biology, Faculty of Science, University of Copenhagen, Denmark
  • Pages: 243-252
    |
    Published online on: May 10, 2016
       https://doi.org/10.3892/ijo.2016.3513
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Abstract

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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Copy and paste a formatted citation
Spandidos Publications style
Zeeberg K, Cardone RA, Greco MR, Saccomano M, Nøhr-Nielsen A, Alves F, Pedersen SF and Reshkin SJ: Assessment of different 3D culture systems to study tumor phenotype and chemosensitivity in pancreatic ductal adenocarcinoma. Int J Oncol 49: 243-252, 2016.
APA
Zeeberg, K., Cardone, R.A., Greco, M.R., Saccomano, M., Nøhr-Nielsen, A., Alves, F. ... Reshkin, S.J. (2016). Assessment of different 3D culture systems to study tumor phenotype and chemosensitivity in pancreatic ductal adenocarcinoma. International Journal of Oncology, 49, 243-252. https://doi.org/10.3892/ijo.2016.3513
MLA
Zeeberg, K., Cardone, R. A., Greco, M. R., Saccomano, M., Nøhr-Nielsen, A., Alves, F., Pedersen, S. F., Reshkin, S. J."Assessment of different 3D culture systems to study tumor phenotype and chemosensitivity in pancreatic ductal adenocarcinoma". International Journal of Oncology 49.1 (2016): 243-252.
Chicago
Zeeberg, K., Cardone, R. A., Greco, M. R., Saccomano, M., Nøhr-Nielsen, A., Alves, F., Pedersen, S. F., Reshkin, S. J."Assessment of different 3D culture systems to study tumor phenotype and chemosensitivity in pancreatic ductal adenocarcinoma". International Journal of Oncology 49, no. 1 (2016): 243-252. https://doi.org/10.3892/ijo.2016.3513
Copy and paste a formatted citation
x
Spandidos Publications style
Zeeberg K, Cardone RA, Greco MR, Saccomano M, Nøhr-Nielsen A, Alves F, Pedersen SF and Reshkin SJ: Assessment of different 3D culture systems to study tumor phenotype and chemosensitivity in pancreatic ductal adenocarcinoma. Int J Oncol 49: 243-252, 2016.
APA
Zeeberg, K., Cardone, R.A., Greco, M.R., Saccomano, M., Nøhr-Nielsen, A., Alves, F. ... Reshkin, S.J. (2016). Assessment of different 3D culture systems to study tumor phenotype and chemosensitivity in pancreatic ductal adenocarcinoma. International Journal of Oncology, 49, 243-252. https://doi.org/10.3892/ijo.2016.3513
MLA
Zeeberg, K., Cardone, R. A., Greco, M. R., Saccomano, M., Nøhr-Nielsen, A., Alves, F., Pedersen, S. F., Reshkin, S. J."Assessment of different 3D culture systems to study tumor phenotype and chemosensitivity in pancreatic ductal adenocarcinoma". International Journal of Oncology 49.1 (2016): 243-252.
Chicago
Zeeberg, K., Cardone, R. A., Greco, M. R., Saccomano, M., Nøhr-Nielsen, A., Alves, F., Pedersen, S. F., Reshkin, S. J."Assessment of different 3D culture systems to study tumor phenotype and chemosensitivity in pancreatic ductal adenocarcinoma". International Journal of Oncology 49, no. 1 (2016): 243-252. https://doi.org/10.3892/ijo.2016.3513
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