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.
Funder
Science Foundation Ireland
Pancreatic Cancer Research Fund
Marie Sklodowska-Curie
Reference59 articles.
1. Projecting cancer incidence and deaths to 2030: The unexpected burden of thyroid, liver, and pancreas cancers in the United States;Rahib;Cancer Res.,2014
2. Cancer statistics, 2016;Siegel;CA Cancer J. Clin.,2016
3. Ushio, J., Kanno, A., Ikeda, E., Ando, K., Nagai, H., Miwata, T., Kawasaki, Y., Tada, Y., Yokoyama, K., and Numao, N. (2021). Pancreatic Ductal Adenocarcinoma: Epidemiology and Risk Factors. Diagnostics, 11.
4. Surgical and molecular pathology of pancreatic neoplasms;Hackeng;Diagn. Pathol.,2016
5. Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma;Raphael;Cancer Cell,2017
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献