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Pancreatic cancer 3D cell line organoids (CLOs) maintain the phenotypic characteristics of organoids and accurately reflect the cellular architecture and heterogeneity In vivo

Noorani, Sara, Nelson, Shannon R. orcid logoORCID: 0000-0003-3014-6679, Conlon, Neil T. orcid logoORCID: 0000-0001-5921-7114, Meiller, Justine, Shcheglova, Ekaterina orcid logoORCID: 0000-0003-3163-9782, Usai, Alice orcid logoORCID: 0000-0003-0226-837X, Stoof, Jojanneke orcid logoORCID: 0000-0002-8331-1597, Palanga, Letizia orcid logoORCID: 0000-0002-8331-1597, O'Neill, Fiona, Roche, Sandra orcid logoORCID: 0000-0002-4363-4607, Cotter, Maura B., Swan, Niall and Walsh, Naomi orcid logoORCID: 0000-0002-2178-3564 (2022) Pancreatic cancer 3D cell line organoids (CLOs) maintain the phenotypic characteristics of organoids and accurately reflect the cellular architecture and heterogeneity In vivo. Organoids, 1 (2). pp. 168-183. ISSN 2674-1172

Abstract
Pancreatic cancer is a highly lethal disease. Therapeutic resistance to chemotherapy is a major cause of treatment failure and recurrence in pancreatic cancer. Organoids derived from cancer stem cells (CSC) are promising models for the advancement of personalised therapeutic responses to inform clinical decisions. However, scaling-up of 3D organoids for high-throughput screening is time-consuming and costly. Here, we successfully developed organoid-derived cell lines (2.5D) from 3D organoids; the cells were then expanded and recapitulated back into organoids known as cell line organoids (CLOs). The 2.5D lines were cultured long term into 2D established cell lines for downstream comparison analysis. Experimental characterisation of the models revealed that the proliferation of CLOs was slightly faster than that of parental organoids. The therapeutic response to chemotherapeutic agents in 3D CLOs and organoids showed a similar responsive profile. Compared to 3D CLOs and organoids, 2D cell lines tended to be less responsive to all the drugs tested. Stem cell marker expression was higher in either 3D CLOs or organoids compared to 2D cell lines. An in vivo tumorigenicity study found CLOs form tumours at a similar rate to organoids and retain enhanced CSC marker expression, indicating the plasticity of CSCs within the in vivo microenvironment.
Metadata
Item Type:Article (Published)
Refereed:Yes
Uncontrolled Keywords:cancer; onlcology; 2.5D organoids; 3D organoids; cell line organoids (CLOs); cancer stem cells; pancreatic cancer; drug resistance
Subjects:Biological Sciences > Cell biology
DCU Faculties and Centres:DCU Faculties and Schools > Faculty of Science and Health > School of Biotechnology
Research Initiatives and Centres > National Institute for Cellular Biotechnology (NICB)
Official URL:https://doi.org/10.3390/organoids1020013
Copyright Information:© 2022 The Authors.
Funders:Science Foundation Ireland (SFI) under the Starting Investigator Research Grant (SIRG) Programme [Grant number 15/SIRG/3482], Pancreatic Cancer Research Fund., PRECODE (the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement Nº 861196)
ID Code:28458
Deposited On:29 Jun 2023 10:49 by Naomi Walsh . Last Modified 29 Jun 2023 11:07
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