Analysis of sialyl-Lewis x on MUC5AC and MUC1 mucins in pancreatic cancer tissues

作者：Balmana Meritxell; Duran Adria; Gomes Catarina; Llop Esther; Lopez Martos Raquel; Rosa Ortiz M; Barrabes Silvia; Reis Celso A^*; Peracaula Rosa^*

来源：International Journal of Biological Macromolecules, 2018, 112: 33-45.

DOI：10.1016/j.ijbiomac.2018.01.148

• Mucins
• Pancreatic cancer
• Sialyl-Lewis x

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 (SLe(x)) 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 SLe(x) 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-SLe(x) and MUC5AC-SLe(x) were found in 68% and 84% respectively, of the mucin expressing PDAC tissues, while STn hardly colocalized with any of the evaluated mudns. Further analysis by Western blot of MUC5AC and SLe(x) 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 SLe(x) immunodetection confirmed the presence of SLe(x) on MUC5AC. Altogether, MUC5AC-SLe(x) glycoform is present in PDAC and can be regarded as potential biomarker.

• 出版日期2018-6