Journal
NATURE MATERIALS
Volume 21, Issue 1, Pages 110-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41563-021-01085-1
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Funding
- Cancer Research UK Program [C13329/A21671]
- Cancer Research UK Institute [A19258, A17196]
- Experimental Medicine Programme Award [A25236]
- Rosetrees Trust [M286]
- European Research Council [ERC-2017-COG 772577]
- National Science Foundation [CBET-0939511]
- National Institutes of Health [R01EB021908, T32GM008334]
- Defense Advanced Research Projects Agency [W911NF-12-2-0039]
- Deutsche Forschungsgemeinschaft (DFG) [SFB1009]
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A synthetic hydrogel has been developed to mimic the physicochemical properties of pancreatic tissue and is shown to support the culture of pancreatic cancer organoids, revealing the role of laminin-integrin interactions in their growth.
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 alpha(3)/alpha(6) 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. A synthetic hydrogel has been developed to mimic the physicochemical properties of pancreatic tissue and is shown to support the culture of pancreatic cancer organoids, revealing the role of laminin-integrin interactions in their growth.
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