The O-Linked Glycome and Blood Group Antigens ABO on Mucin-Type Glycoproteins in Mucinous and Serous Epithelial Ovarian Tumors (original) (raw)
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The CA125 assay detects circulating MUC16 and is one of the most widely used cancer biomarkers for the follow-up of ovarian cancer. We previously demonstrated that detection of aberrant cancer-associated glycoforms of MUC16 as well as MUC1 in circulation could improve the yield of these serum assays. Our aim was to refine ovarian cancer biomarkers by detection of aberrant glycoforms (Tn, STn, and T) of MUC16 and MUC1 in ovarian cancer tissue using Proximity Ligation Assays (PLA). We studied two series of serous ovarian tumours, a pilot series of 66 ovarian tumours (27 cystadenomas, 16 borderline tumours and 23 adenocarcinomas) from Centro Hospitalar S. João, Porto and a validation series of 89 ovarian tumours (17 cystadenomas, 25 borderline tumours and 47 adenocarcinomas) from the Portuguese Institute of Oncology Francisco Gentil, Lisbon. PLA reactions for MUC16/Tn, MUC16/STn, MUC1/Tn and MUC1/STn were negative in benign lesions but often positive in borderline and malignant lesions...
MUCINS: POTENTIAL FOR OVARIAN CANCER BIOMARKERS
Mucins comprise a wide range of proteins which generally expresses at the cell surface, heavily glycosylated and functions as providing the protection to the cell membrane. It is now reported that aberrant form of mucins is generally related with the pathogenesis of a number of cancer, including ovarian cancer. This review is focuses on the role of mucin as potential biomarker for the ovarian cancer.
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Ovarian cancer tissue contains highly sulfated O-glycoproteins. • Sulfation occurs on GlcNAc (6-position) and Gal (3-and 6-position). • Sulfation of Gal can be mimicked recombinantly with selected sulfotransferase. • The Gal3ST2 sulfotransferase level is lower in malignant cancer compared with benign.
Acute-phase glycoprotein N-glycome of ovarian cancer patients analyzed by CE-LIF
Electrophoresis, 2016
Epithelial ovarian cancer (EOC) is the most frequent cause of death from all gynecological malignancies because of its late diagnosis. As N-glycosylation is modified in the course of ovarian cancer, it is a promising source of tumor biomarkers. In this work, serum glycoproteins, depleted from albumin and IgG, were separated by 2DE. Protein spots of acute-phase proteins were identified by peptide mapping and their corresponding glycan moieties were released enzymatically, fluorescently labeled and analyzed by CE-LIF. In the positive acute-phase proteins haptoglobin, α1-antitrypsin and α1-antichymotrypsin, an increase of antennarity and Lewis(X) motif could be measured in EOC patients on tri- and/or tetraantennary N-glycans. Tetraantennary N-glycans containing three Lewis(X) epitopes and triantennary N-glycans containing a β(1-6) branch and a Lewis(X) epitope were only present in EOC patients. We also showed for the first time that the core-fucosylated biantennary digalactosylated N-g...
International Journal of Molecular Sciences, 2013
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Mucin Gene Expression in Ovarian Cancers1
1998
Ovarian cancer ¡s a highly lethal disease with métastasespresent in the majority of patients at the time of diagnosis. The molecular mechanisms underlying the metastatic process of this cancer are not well understood. One family of cell-associated and secreted glycoproteins, the mucin glycoproteins, has been implicated in events leading to metastasis of several epithelial cancers including gastrointestinal and lung cancers. The pur pose of this study was to characterize mucin gene expression in ovarian cancers and relate expression to tumor histology, stage, and patient sur vival. RNA was isolated from 29 epithelial ovarian cancers, 1 neuroendocrine carcinoma, 3 mixed mesoderma! tumors, and two transformed, yet nonmalignant, ovarian epithelial cell lines. The expression of mucin genes, and SB, was determined by northern analyses. Epithelial ovarian cancers expressed several mucins including .\ll'('\. 2,4, and SAC; MUC3 and SB were rarely expressed. In contrast, the trans formed nonmalignant ovarian epithelial cell lines expressed only MUCl and SAC. Although there was no correlation of mucin expression with tumor histology, there was a significant decrease in expression of MUC3 and l/f/4 with increasing cancer stage (/" < 0.05). In addition, a trend toward improved patient survival occurred with increased expression of MUC4. These observations suggest a relationship between mucin gene expression and the metastatic process in epithelial ovarian cancers. Ad ditional investigation of MUCÃOE and MUC4 in ovarian cancers may lead to new approaches for early detection and therapy.
Journal of Cellular and Molecular Medicine, 2012
Mucin glycoproteins are major secreted or membrane-bound molecules that, in cancer, show modifications in both the mucin proteins expression and in the O-glycosylation profile, generating some of the most relevant tumour markers in clinical use for decades. Thus far, the identification of these biomarkers has been based on the detection of either the protein or the O-glycan modifications. We therefore aimed to identify the combined mucin and O-glycan features, that is, specific glycoforms, in an attempt to increase specificity of these cancer biomarkers. Using in situ proximity ligation assays (PLA) based on existing monoclonal antibodies directed to MUC1, MUC2, MUC5AC and MUC6 mucins and to cancer-associated carbohydrate antigens Tn, Sialyl-Tn (STn), T, Sialyl-Le a (SLe a) and Sialyl-Le x (SLe x) we screened a series of 28 mucinous adenocarcinomas from different locations (stomach, ampulla of Vater, colon, lung, breast and ovary) to detect specific mucin glycoforms. We detected Tn/STn/SLe a /SLe x-MUC1 and STn/SLe a /SLe x-MUC2 glycoforms in Ն50% of the cases, with a variable distribution among organs. Some new glycoforms-T/SLe a-MUC2, STn/T/SLe a /SLe x-MUC5AC and STn/T/SLe a /SLe x-MUC6-were identified for the first time in the present study in a variable percentage of cases from different organs. In conclusion, application of the PLA technique allowed sensitive detection of specific aberrant mucin glycoforms in cancer, increasing specificity to the use of antibodies either to the mucin protein backbone or to the O-glycan haptens alone.
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Journal of Ovarian Research, 2009
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