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Carcinoembryonic antigen is a sialyl Lewis x/a carrier and an E‑selectin ligand in non‑small cell lung cancer

2019-01-01Artigo científico Acesso aberto
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dc.contributor.authorFerreira, Inês Gomes
dc.contributor.authorCarrascal, Mylène
dc.contributor.authorMineiro, A. Gonçalo
dc.contributor.authorBugalho, António
dc.contributor.authorBorralho, Paula
dc.contributor.authorSilva, Zélia
dc.contributor.authorDall'Olio, Fabio
dc.contributor.authorVideira, Paula A.
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.institutionCentro de Estudos de Doenças Crónicas (CEDOC)
dc.contributor.institutionUCIBIO - Applied Molecular Biosciences Unit
dc.contributor.institutionDCV - Departamento de Ciências da Vida
dc.contributor.pblSpandidos Publications
dc.date.accessioned2021-03-30T22:18:33Z
dc.date.available2021-03-30T22:18:33Z
dc.date.issued2019-01-01
dc.descriptionLPCC/Pfizer 2011. Tagus TANK award 2018 (grant no. 1/2018). SFRH/BD/100970/2014 SFRH/BPD/108686/2015
dc.description.abstractThe formation of distant metastasis resulting from vascular dissemination is one of the leading causes of mortality in non-small cell lung cancer (NSCLC). This metastatic dissemination initiates with the adhesion of circulating cancer cells to the endothelium. The minimal requirement for the binding of leukocytes to endothelial E-selectins and subsequent transmigration is the epitope of the fucosylated glycan, sialyl Lewis x (sLex), attached to specific cell surface glycoproteins. sLex and its isomer sialyl Lewis a (sLea) have been described in NSCLC, but their functional role in cancer cell adhesion to endothelium is still poorly understood. In this study, it was hypothesised that, similarly to leukocytes, sLe glycans play a role in NSCLC cell adhesion to E-selectins. To assess this, paired tumour and normal lung tissue samples from 18 NSCLC patients were analyzed. Immunoblotting and immunohistochemistry assays demonstrated that tumour tissues exhibited significantly stronger reactivity with anti‑sLex/sLea antibody and E-selectin chimera than normal tissues (2.2- and 1.8-fold higher, respectively), as well as a higher immunoreactive score. High sLex/sLea expression was associated with bone metastasis. The overall α1,3-fucosyltransferase (FUT) activity was increased in tumour tissues, along with the mRNA levels of FUT3, FUT6 and FUT7, whereas FUT4 mRNA expression was decreased. The expression of E-selectin ligands exhibited a weak but significant correlation with the FUT3/FUT4 and FUT7/FUT4 ratios. Additionally, carcinoembryonic antigen (CEA) was identified in only 8 of the 18 tumour tissues; CEA-positive tissues exhibited significantly increased sLex/sLea expression. Tumour tissue areas expressing CEA also expressed sLex/sLea and showed reactivity to E-selectin. Blot rolling assays further demonstrated that CEA immunoprecipitates exhibited sustained adhesive interactions with E-selectin-expressing cells, suggesting CEA acts as a functional protein scaffold for E-selectin ligands in NSCLC. In conclusion, this work provides the first demonstration that sLex/sLea are increased in primary NSCLC due to increased α1,3-FUT activity. sLex/sLea is carried by CEA and confers the ability for NSCLC cells to bind E-selectins, and is potentially associated with bone metastasis. This study contributes to identifying potential future diagnostic/prognostic biomarkers and therapeutic targets for lung cancer.en
dc.description.versionpreprint
dc.description.versionpublished
dc.format.extent16
dc.format.extent321429
dc.identifier.doi10.3892/ijo.2019.4886
dc.identifier.issn1019-6439
dc.identifier.otherPURE: 15006000
dc.identifier.otherPURE UUID: b9bdb836-1c1e-4c81-96b1-489ef618c80a
dc.identifier.otherScopus: 85072794933
dc.identifier.otherORCID: /0000-0001-5987-2485/work/64041217
dc.identifier.otherORCID: /0000-0001-6660-426X/work/203333199
dc.identifier.urihttp://hdl.handle.net/10362/114758
dc.identifier.urlhttps://www.scopus.com/pages/publications/85072794933
dc.language.isoeng
dc.peerreviewedyes
dc.subjectCEA
dc.subjectMetastasis
dc.subjectNSCLC
dc.subjectSelectin ligands
dc.subjectOncology
dc.subjectCancer Research
dc.subjectSDG 3 - Good Health and Well-being
dc.titleCarcinoembryonic antigen is a sialyl Lewis x/a carrier and an E‑selectin ligand in non‑small cell lung canceren
dc.typejournal article
degois.publication.firstPage1033
degois.publication.issue5
degois.publication.lastPage1048
degois.publication.titleInternational Journal Of Oncology
degois.publication.volume55
dspace.entity.typePublication
rcaap.rightsopenAccess

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