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dc.contributor.authorRodenhizer, Darrenen
dc.contributor.authorGaude, Edoardoen
dc.contributor.authorCojocari, Danen
dc.contributor.authorMahadevan, Radhakrishnanen
dc.contributor.authorFrezza, Christianen
dc.contributor.authorWouters, Bradly Gen
dc.contributor.authorMcGuigan, Alison Pen
dc.date.accessioned2015-11-26T12:24:10Z
dc.date.available2015-11-26T12:24:10Z
dc.date.issued2015-11-23en
dc.identifier.citationRodenhizer et al. Nature Materials (2015) Vol. 15, pp. 227-234. doi: 10.1038/nmat4482en
dc.identifier.issn1476-1122
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/252752
dc.description.abstractThe profound metabolic reprogramming that occurs in cancer cells has been investigated primarily in two-dimensional cell cultures, which fail to recapitulate spatial aspects of cell-to-cell interactions as well as tissue gradients present in three-dimensional tumours. Here, we describe an engineered model to assemble three-dimensional tumours by rolling a scaffold–tumour composite strip. By unrolling the strip, the model can be rapidly disassembled for snapshot analysis, allowing spatial mapping of cell metabolism in concert with cell phenotype. We also show that the establishment of oxygen gradients within samples that are shaped by oxygen-dependent signalling pathways, as well as the consequential variations in cell growth, response to hypoxic gradients extending from normoxia to severe hypoxia, and therapy responsiveness, are consistent with those of tumours in vivo. Moreover, by using liquid chromatography tandem mass spectrometry, we mapped cellular metabolism and identified spatially defined metabolic signatures of cancer cells to reveal both known and novel metabolic responses to hypoxia.
dc.description.sponsorshipThe authors acknowledge V. Bindokas (University of Chicago), M. Macasaet-Peralta (Pathology Research Program, UHN), J. Cathcart (AOMF), J. Stewart and D. Scollard (STTARR), B. Calvieri, S. Doyle, J. Soleas, S. Javaherian, C. Londono, C. Crossman, R. Vellanki, J. Han, M. Young and S. Lakhani (University of Toronto) for technical assistance. This work was funded by a Natural Science and Engineering Council Discovery Accelerator Supplement (RGPIN-314056) to A.P.M., a YSF NSERC fellowship to D.R., MRC Cancer Unit Core Funding to C.F. and E.G., Ontario Ministry of Health and Long Term Care (OMOHLTC), the Terry Fox New Frontiers Research Program (PPG09-020005) and the Canadian Institute for Health Research (CIHR grant 201592) grants to B.G.W., and by a Ontario Graduate Scholarship to D.C.
dc.languageEnglishen
dc.language.isoenen
dc.publisherNature Publishing Group
dc.subjectBiomaterials – cellsen
dc.subjectBiomedical engineeringen
dc.subjectGels and hydrogelsen
dc.subjectTissuesen
dc.titleA three-dimensional engineered tumour for spatial snapshot analysis of cell metabolism and phenotype in hypoxic gradientsen
dc.typeArticle
dc.description.versionThis is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nmat4482en
prism.endingPage234
prism.publicationDate2015en
prism.publicationNameNature Materialsen
prism.startingPage227
prism.volume15en
dc.rioxxterms.funderMRC
dcterms.dateAccepted2015-10-20en
rioxxterms.versionofrecord10.1038/nmat4482en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-11-23en
dc.contributor.orcidFrezza, Christian [0000-0002-3293-7397]
dc.identifier.eissn1476-4660
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMedical Research Council (MC_UU_12022/6)
pubs.funder-project-idMRC (MC_UU_12022/1_do not transfer?)
rioxxterms.freetoread.startdate2016-05-23


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