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Published March 20, 2021 | Version 12_2020_V1
Journal article Open

A microenvironment-inspired synthetic 3D model for pancreatic ductal adenocarcinoma organoids

  • 1. Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, SK10 4TG, Manchester, UK
  • 2. Centre for Gynepathology Research, Massachusetts Institute of Technology, MA 02139, Cambridge, USA
  • 3. Wellcome Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, The University of Manchester, M13 9PT, Manchester, UK
  • 4. Manchester Royal Infirmary, Oxford Road, M13 9WL, Manchester, UK
  • 5. Institute for Physiological Chemistry und Pathobiochemistry, University of Muenster, Waldeyerstrasse 15, 48149 Muenster, GER
  • 6. BioAFM Facility, Faculty of Biology, Medicine and Health, The University of Manchester, M13 9PT, Manchester, UK
  • 7. Biological Mass Spectrometry Core Facility, Faculty of Biology, Medicine and Health, The University of Manchester, M13 9PT, Manchester, UK
  • 8. EM Core Facility, Faculty of Biology, Medicine and Health, The University of Manchester, M13 9PT, Manchester, UK
  • 9. Cancer Research UK Beatson Institute, Switchback Rd, Garscube Estate, Bearsden, Glasgow, G61 1BD, UK

Description

Experimental in vitro models that accurately capture pathophysiological characteristics of human tumours are essential for basic and translational cancer biology. Here, we describe a fully synthetic hydrogel extracellular matrix, specifically designed to elicit key phenotypic traits of the pancreatic environment in culture. To enable the growth of normal and cancerous pancreatic organoids from murine genetically engineered models and human patients, essential adhesive cues were empirically defined and incorporated into the hydrogel scaffold, revealing a functional role of laminin – integrin a3/a6 signalling in adhesion and survival of pancreatic organoids. Altered tissue stiffness — a hallmark of pancreatic cancer — was recapitulated in culture by adjusting the hydrogel properties to engage mechano-signalling and alter organoid growth. Pancreatic stromal cells were readily incorporated and replicated phenotypic traits characteristic of the tumour environment in vivo. This model therefore recapitulates a pathologically remodelled tumour microenvironment for studies of normal and pancreatic cancer cells in vitro. 

Notes

This upload is compiled of 21 individual data packages which contain the raw data and R-scripts necessary to generate the outputs displayed in the paper. Each folder contains a README document which assists the reader through the files.

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Additional details

Related works

Is supplemented by
Dataset: 10.6019/PXD022555 (DOI)
Dataset: 10.6019/PXD022487 (DOI)
Dataset: 10.6019/PXD022509 (DOI)
Dataset: 10.6019/PXD02252 (DOI)
Dataset: 10.6019/PXD022767 (DOI)