Modelling of pancreatic cancer biology: transcriptomic signature for 3D PDX-derived organoids and primary cell line organoid development

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Shannon R Nelson, National Institute for Cellular Biotechnology, School of Biotechnology, Dublin City University, Dublin 9, Ireland.
  • ,
  • Chenxi Zhang, Lars Bolund Institute of Regenerative Medicine, BGI-Qingdao, BGI-Shenzhen, Qingdao, 266000, China.
  • ,
  • Sandra Roche, National Institute for Cellular Biotechnology, School of Biotechnology, Dublin City University, Dublin 9, Ireland.
  • ,
  • Fiona O'Neill, National Institute for Cellular Biotechnology, School of Biotechnology, Dublin City University, Dublin 9, Ireland.
  • ,
  • Niall Swan, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
  • ,
  • Yonglun Luo
  • AnneMarie Larkin, Institute of Technology, Sligo, Ash Lane, Sligo, Ireland.
  • ,
  • John Crown, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
  • ,
  • Naomi Walsh, National Institute for Cellular Biotechnology, School of Biotechnology, Dublin City University, Dublin 9, Ireland. naomi.walsh@dcu.ie.

With a five-year survival rate of 9%, pancreatic ductal adenocarcinoma (PDAC) is the deadliest of all cancers. The rapid mortality makes PDAC difficult to research, and inspires a resolve to create reliable, tractable cellular models for preclinical cancer research. Organoids are increasingly used to model PDAC as they maintain the differentiation status, molecular and genomic signatures of the original tumour. In this paper, we present novel methodologies and experimental approaches to develop PDAC organoids from PDX tumours, and the simultaneous development of matched primary cell lines. Moreover, we also present a method of recapitulating primary cell line cultures to organoids (CLOs). We highlight the usefulness of CLOs as PDAC organoid models, as they maintain similar transcriptomic signatures as their matched patient-derived organoids and patient derived xenografts (PDX)s. These models provide a manageable, expandable in vitro resource for downstream applications such as high throughput screening, functional genomics, and tumour microenvironment studies.

Original languageEnglish
Article number2778
JournalScientific Reports
Volume10
Issue1
Number of pages10
ISSN2045-2322
DOIs
Publication statusPublished - 2020

See relations at Aarhus University Citationformats

ID: 179652774