Please use this identifier to cite or link to this item: https://hdl.handle.net/10216/119038
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dc.creatorCampos, D
dc.creatorFreitas, D
dc.creatorGomes, J
dc.creatorMagalhães, A
dc.creatorSteentoft, C
dc.creatorGomes, C
dc.creatorVester-Christensen, M
dc.creatorFerreira, JA
dc.creatorAfonso, L
dc.creatorSantos, L
dc.creatorSousa, J
dc.creatorMandel, U
dc.creatorClausen, H
dc.creatorVakhrushev, S
dc.creatorReis, CA
dc.date.accessioned2019-02-21T12:16:19Z-
dc.date.available2019-02-21T12:16:19Z-
dc.date.issued2015
dc.identifier.issn1535-9476
dc.identifier.urihttps://hdl.handle.net/10216/119038-
dc.description.abstractCirculating O-glycoproteins shed from cancer cells represent important serum biomarkers for diagnostic and prognostic purposes. We have recently shown that selective detection of cancer-associated aberrant glycoforms of circulating O-glycoprotein biomarkers can increase specificity of cancer biomarker assays. However, the current knowledge of secreted and circulating O-glycoproteins is limited. Here, we used the COSMC KO "Simple- Cell" (SC) strategy to characterize the O-glycoproteome of two gastric cancer SimpleCell lines (AGS, MKN45) as well as a gastric cell line (KATO III) which naturally expresses at least partially truncated O-glycans. Overall, we identified 499 O-glycoproteins and 1236 O-glycosites in gastric cancer SimpleCells, and a total 47 O-glycoproteins and 73 O-glycosites in the KATO III cell line. We next modified the glycoproteomic strategy to apply it to pools of sera from gastric cancer and healthy individuals to identify circulating O-glycoproteins with the STn glycoform. We identified 37 O-glycoproteins in the pool of cancer sera, and only nine of these were also found in sera from healthy individuals. Two identified candidate O-glycoprotein biomarkers (CD44 and GalNAc-T5) circulating with the STn glycoform were further validated as being expressed in gastric cancer tissue. A proximity ligation assay was used to show that CD44 was expressed with the STn glycoform in gastric cancer tissues. The study provides a discovery strategy for aberrantly glycosylated O-glycoproteins and a set of O-glycoprotein candidates with biomarker potential in gastric cancer.
dc.description.sponsorshipThis work was supported by The Danish Research Councils, The Mizutani Foundation, The Danish National Research Foundation (DNRF107) and Fundacão para a Ciência e a Tecnologia (FCT) and COMPETE (Programa Operacional Temático Factores de Competitividade, comparticipado pelo fundo comunitário europeu FEDER) in the framework of the projects: PTDC/BBB-EBI/0786/2012; EXPL/CTM-BIO/0762/2013. Grants were received from FCT (SFRH/BD/73717/2010 to DC), (SFRH/BPD/75871/2011 to AM), (SFRH/BPD/96510/2013 to CG) and (SFRH/BPD/66288/2009 to JAF). IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education, and is partially supported by FCT.
dc.language.isoeng
dc.publisherAmerican Society for Biochemistry and Molecular Biology
dc.relationinfo:eu-repo/grantAgreement/FCT/COMPETE/125428/PT
dc.relationinfo:eu-repo/grantAgreement/FCT/COMPETE/133784/PT
dc.relationinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F73717%2F2010/PT
dc.relationinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F75871%2F2011/PT
dc.relationinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F96510%2F2013/PT
dc.relationinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F66288%2F2009/PT
dc.relation.ispartofMolecular and Cellular Proteomics, vol.14(6), p. 1616-1629
dc.rightsopenAccess
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectBiomarkers, Tumor/blood
dc.subjectBiomarkers, Tumor/metabolism
dc.subjectCell Line, Tumor
dc.subjectFemale
dc.subjectGlycoproteins/blood
dc.subjectGlycoproteins/metabolism
dc.subjectHumans
dc.subjectMale
dc.subjectMiddle Aged
dc.subjectN-Acetylgalactosaminyltransferases/blood
dc.subjectN-Acetylgalactosaminyltransferases/metabolism
dc.subjectProteome
dc.subjectStomach Neoplasms/blood
dc.subjectStomach Neoplasms/metabolism
dc.titleProbing the O-glycoproteome of gastric cancer cell lines for biomarker discovery
dc.typeArtigo em Revista Científica Internacional
dc.contributor.uportoInstituto de Investigação e Inovação em Saúde
dc.identifier.doi10.1074/mcp.M114.046862
dc.relation.publisherversionhttp://www.mcponline.org/content/14/6/1616.long
Appears in Collections:I3S - Artigo em Revista Científica Internacional

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