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    A microenvironment-inspired synthetic three-dimensional model for pancreatic ductal adenocarcinoma organoids

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    Authors
    Below, Christopher R
    Kelly, Joanna
    Brown, A.
    Humphries, J. D.
    Hutton, Colin
    Xu, Jingshu
    Lee, Brian Y
    Cintas, Celia
    Zhang, Xiaohong
    Hernandez-Gordillo, V.
    Stockdale, L.
    Goldsworthy, M. A.
    Geraghty, J.
    Foster, L.
    O'Reilly, D. A.
    Schedding, B.
    Askari, J.
    Burns, J.
    Hodson, N.
    Smith, Duncan L
    Lally, Catherine
    Ashton, Garry
    Knight, D.
    Mironov, A.
    Banyard, Antonia
    Eble, J. A.
    Morton, J. P.
    Humphries, M. J.
    Griffith, L. G.
    Jørgensen, Claus
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    Affiliation
    Cancer Research UK Manchester Institute, The University of Manchester, Manchester, UK
    Issue Date
    2021
    
    Metadata
    Show full item record
    Abstract
    Experimental in vitro models that capture pathophysiological characteristics of human tumours are essential for basic and translational cancer biology. Here, we describe a fully synthetic hydrogel extracellular matrix designed to elicit key phenotypic traits of the pancreatic environment in culture. To enable the growth of normal and cancerous pancreatic organoids from genetically engineered murine models and human patients, essential adhesive cues were empirically defined and replicated in the hydrogel scaffold, revealing a functional role of laminin-integrin α3/α6 signalling in establishment 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-sensing pathways and alter organoid growth. Pancreatic stromal cells were readily incorporated into the hydrogels 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.
    Citation
    Below CR, Kelly J, Brown A, Humphries JD, Hutton C, Xu J, et al. A microenvironment-inspired synthetic three-dimensional model for pancreatic ductal adenocarcinoma organoids. Nat Mater. 2021 Sep 13.
    Journal
    Nature Materials
    URI
    http://hdl.handle.net/10541/624640
    DOI
    10.1038/s41563-021-01085-1
    PubMed ID
    34518665
    Additional Links
    https://dx.doi.org/10.1038/s41563-021-01085-1
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41563-021-01085-1
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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