A microenvironment-inspired synthetic three-dimensional model for pancreatic ductal adenocarcinoma organoids
Authors
Below, Christopher RKelly, 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
Affiliation
Cancer Research UK Manchester Institute, The University of Manchester, Manchester, UKIssue Date
2021
Metadata
Show full item recordAbstract
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 MaterialsDOI
10.1038/s41563-021-01085-1PubMed ID
34518665Additional Links
https://dx.doi.org/10.1038/s41563-021-01085-1Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1038/s41563-021-01085-1
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