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dc.contributor.authorRajcevic, Urosen_US
dc.contributor.authorKnol, Jaco Cen_US
dc.contributor.authorPiersma, Sanderen_US
dc.contributor.authorBougnaud, Sébastienen_US
dc.contributor.authorFack, Freden_US
dc.contributor.authorSundlisæter, Eiriken_US
dc.contributor.authorSøndenaa, Karlen_US
dc.contributor.authorMyklebust, Reidaren_US
dc.contributor.authorPham, Thang V.en_US
dc.contributor.authorNiclou, Simone P.en_US
dc.contributor.authorJiménez, Connie R.en_US
dc.date.accessioned2014-09-11T12:35:20Z
dc.date.available2014-09-11T12:35:20Z
dc.date.issued2014-07-11eng
dc.identifier.issn1477-5956
dc.identifier.urihttps://hdl.handle.net/1956/8449
dc.description.abstractBackground: Organotypic tumor spheroids, a 3D in vitro model derived from patient tumor material, preserve tissue heterogeneity and retain structural tissue elements, thus replicating the in vivo tumor more closely than commonly used 2D and 3D cell line models. Such structures harbour tumorigenic cells, as revealed by xenograft implantation studies in animal models and maintain the genetic makeup of the original tumor material. The aim of our work was a morphological and proteomic characterization of organotypic spheroids derived from colorectal cancer tissue in order to get insight into their composition and associated biology. Results: Morphological analysis showed that spheroids were of about 250 μm in size and varied in structure, while the spheroid cells differed in shape and size and were tightly packed together by desmosomes and tight junctions. Our proteomic data revealed significant alterations in protein expression in organotypic tumor spheroids cultured as primary explants compared to primary colorectal cancer tissue. Components underlying cellular and tissue architecture were changed; nuclear DNA/ chromatin maintenance systems were up-regulated, whereas various mitochondrial components were down-regulated in spheroids. Most interestingly, the mesenchymal cells appear to be substantial component in such cellular assemblies. Thus the observed changes may partly occur in this cellular compartment. Finally, in the proteomics analysis stem cell-like characteristics were observed within the spheroid cellular assembly, reflected by accumulation of Alcam, Ctnnb1, Aldh1, Gpx2, and CD166. These findings were underlined by IHC analysis of Ctnnb1, CD24 and CD44, therefore warranting closer investigation of the tumorigenic compartment in this 3D culture model for tumor tissue. Conclusions: Our analysis of organotypic CRC tumor spheroids has identified biological processes associated with a mixture of cell types and states, including protein markers for mesenchymal and stem-like cells. This 3D tumor model in which tumor heterogeneity is preserved may represent an advantageous model system to investigate novel therapeutic approaches.en_US
dc.language.isoengeng
dc.publisherBioMed Centraleng
dc.rightsAttribution CC BYeng
dc.rights.urihttp://creativecommons.org/licenses/by/2.0eng
dc.subjectColorectal cancereng
dc.subjectTissue spheroidseng
dc.subjectProteomicseng
dc.subjectMass spectrometryeng
dc.subjectCancer stem cellseng
dc.subjectBioinformaticseng
dc.subjectCancer biomarkerseng
dc.subjectLabel-free proteomicseng
dc.subject3D cell cultureseng
dc.titleColorectal cancer derived organotypic spheroids maintain essential tissue characteristics but adapt their metabolism in cultureen_US
dc.typePeer reviewed
dc.typeJournal article
dc.date.updated2014-08-27T11:27:51Z
dc.description.versionpublishedVersionen_US
dc.rights.holderUros Rajcevic et al.; licensee BioMed Central Ltd.
dc.rights.holderCopyright 2014 Rajcevic et al.; licensee BioMed Central Ltd.
dc.source.articlenumber39
dc.identifier.doihttps://doi.org/10.1186/1477-5956-12-39
dc.identifier.cristin1151450
dc.source.journalProteome Science
dc.source.4012


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