Analysis of sialyl-Lewis x on MUC5AC and MUC1 mucins in pancreatic cancer tissues
| Autor: | Esther Llop, Adrià Duran, Celso A. Reis, M. Rosa Ortiz, Catarina Gomes, Rosa Peracaula, Raquel López-Martos, Sílvia Barrabés, Meritxell Balmaña |
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| Přispěvatelé: | Instituto de Investigação e Inovação em Saúde |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Glycosylation endocrine system diseases Oligosaccharides Proximity ligation assay Mucin 5AC Biochemistry Epitope Epitopes chemistry.chemical_compound 0302 clinical medicine Structural Biology MUC1 Aged 80 and over chemistry.chemical_classification biology Chemistry General Medicine Middle Aged respiratory system Sialyl-Lewis x 3. Good health 030220 oncology & carcinogenesis Female Glycan Adenocarcinoma digestive system 03 medical and health sciences Pancreatic cancer Biomarkers Tumor medicine Humans Antigens Tumor-Associated Carbohydrate Sialyl Lewis X Antigen Molecular Biology Aged Neoplasm Staging Mucin-1 Mucin Mucins medicine.disease digestive system diseases Pancreatic Neoplasms 030104 developmental biology Sialyl-Lewis X Cancer research biology.protein Glycoprotein |
| Zdroj: | Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP |
| Popis: | Pancreatic adenocarcinoma (PDAC) lacks efficient biomarkers. Mucins are glycoproteins that can carry aberrant glycosylation in cancer. Our objective was to identify cancer-related glycan epitopes on MUC1 and MUC5AC mucins in PDAC as potential biomarkers. We have analysed the tumour-associated carbohydrate antigens sialyl-Lewis x (SLex) and sialyl-Tn (STn) on MUC1 and MUC5AC in PDAC tissues. The selected cohort for this study consisted of twenty-one PDAC tissues positive for SLex antigen and three normal pancreas specimens as controls. STn expression was shown in 76% of the PDAC tissues. MUC1 and MUC5AC were detected in 90% of PDAC tissues. We performed in situ proximity ligation assay combining antibodies against mucins and glycan epitopes to identify specific mucin glycoforms. MUC1-SLex and MUC5AC-SLex were found in 68% and 84% respectively, of the mucin expressing PDAC tissues, while STn hardly colocalized with any of the evaluated mucins. Further analysis by Western blot of MUC5AC and SLex in eight PDAC tissue lysates showed that six out of eight cases were positive for both markers. Moreover, immunoprecipitation of MUC5AC from positive PDAC tissues and subsequent SLex immunodetection confirmed the presence of SLex on MUC5AC. Altogether, MUC5AC-SLex glycoform is present in PDAC and can be regarded as potential biomarker. M.B. acknowledges University of Girona for a pre-doctoral fellowship and a mobility grant. We also thank David Carreras for part of the IHC analysis. The authors also thank Dr. Carme de Bolós from Gastroesophagic Cancer Research Group, Hospital del Mar Medical Research Institute (IMIM), for kindly providing anti-MUC5AC rabbit polyclonal antibody Lum5.1. This work was supported by Spanish Ministry of Science and Innovation (grant BIO 2015-66356-R, awarded to R.P.). C.A.R. acknowledges the support by Gastric Glyco Explorer Initial Training Network (Seventh Framework Programme, project GastricGlycoExplorer, grant number 316929), and Fundação para a Ciência e Tecnologia, project PTDC/BBBEBI/0567/2014 (POCI-010145-FEDER-016585) and NORTE 2020 (NORTE-01-0145-FEDER-000029). |
| Databáze: | OpenAIRE |
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