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Identification of new cancer biomarkers based on aberrant mucin glycoforms by in situ proximity ligation

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 biom...

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Autores principales: Pinto, Rita, Carvalho, Ana S, Conze, Tim, Magalhães, Ana, Picco, Gianfranco, Burchell, Joy M, Taylor-Papadimitriou, Joyce, Reis, Celso A, Almeida, Raquel, Mandel, Ulla, Clausen, Henrik, Söderberg, Ola, David, Leonor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823216/
https://www.ncbi.nlm.nih.gov/pubmed/21883895
http://dx.doi.org/10.1111/j.1582-4934.2011.01436.x
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author Pinto, Rita
Carvalho, Ana S
Conze, Tim
Magalhães, Ana
Picco, Gianfranco
Burchell, Joy M
Taylor-Papadimitriou, Joyce
Reis, Celso A
Almeida, Raquel
Mandel, Ulla
Clausen, Henrik
Söderberg, Ola
David, Leonor
author_facet Pinto, Rita
Carvalho, Ana S
Conze, Tim
Magalhães, Ana
Picco, Gianfranco
Burchell, Joy M
Taylor-Papadimitriou, Joyce
Reis, Celso A
Almeida, Raquel
Mandel, Ulla
Clausen, Henrik
Söderberg, Ola
David, Leonor
author_sort Pinto, Rita
collection PubMed
description 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 $50% 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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spelling pubmed-38232162015-03-27 Identification of new cancer biomarkers based on aberrant mucin glycoforms by in situ proximity ligation Pinto, Rita Carvalho, Ana S Conze, Tim Magalhães, Ana Picco, Gianfranco Burchell, Joy M Taylor-Papadimitriou, Joyce Reis, Celso A Almeida, Raquel Mandel, Ulla Clausen, Henrik Söderberg, Ola David, Leonor J Cell Mol Med Original Articles 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 $50% 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. Blackwell Publishing Ltd 2012-07 2012-06-28 /pmc/articles/PMC3823216/ /pubmed/21883895 http://dx.doi.org/10.1111/j.1582-4934.2011.01436.x Text en Copyright © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
spellingShingle Original Articles
Pinto, Rita
Carvalho, Ana S
Conze, Tim
Magalhães, Ana
Picco, Gianfranco
Burchell, Joy M
Taylor-Papadimitriou, Joyce
Reis, Celso A
Almeida, Raquel
Mandel, Ulla
Clausen, Henrik
Söderberg, Ola
David, Leonor
Identification of new cancer biomarkers based on aberrant mucin glycoforms by in situ proximity ligation
title Identification of new cancer biomarkers based on aberrant mucin glycoforms by in situ proximity ligation
title_full Identification of new cancer biomarkers based on aberrant mucin glycoforms by in situ proximity ligation
title_fullStr Identification of new cancer biomarkers based on aberrant mucin glycoforms by in situ proximity ligation
title_full_unstemmed Identification of new cancer biomarkers based on aberrant mucin glycoforms by in situ proximity ligation
title_short Identification of new cancer biomarkers based on aberrant mucin glycoforms by in situ proximity ligation
title_sort identification of new cancer biomarkers based on aberrant mucin glycoforms by in situ proximity ligation
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823216/
https://www.ncbi.nlm.nih.gov/pubmed/21883895
http://dx.doi.org/10.1111/j.1582-4934.2011.01436.x
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