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

Rita Pinto; Ana S Carvalho; Tim Conze; Ana Magalhães; Gianfranco Picco; Joy M Burchell; Joyce Taylor-Papadimitriou; Celso A Reis; Raquel Almeida; Ulla Mandel; Henrik Clausen; Ola Söderberg; Leonor David

doi:10.1111/j.1582-4934.2011.01436.x

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

Rita Pinto, Ana S Carvalho, Tim Conze, Ana Magalhães, Gianfranco Picco, Joy M Burchell, Joyce Taylor-Papadimitriou, Celso A Reis, Raquel Almeida, Ulla Mandel, Henrik Clausen, Ola Söderberg, Leonor David

59 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Journal of Cellular and Molecular Medicine
Volume	16
Issue number	7
Pages (from-to)	1474-1484
Number of pages	11
ISSN	1582-1838
DOIs	https://doi.org/10.1111/j.1582-4934.2011.01436.x
Publication status	Published - Jul 2012

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Pinto, R., Carvalho, A. S., Conze, T., Magalhães, A., Picco, G., Burchell, J. M., Taylor-Papadimitriou, J., Reis, C. A., Almeida, R., Mandel, U., Clausen, H., Söderberg, O., & David, L. (2012). Identification of new cancer biomarkers based on aberrant mucin glycoforms by in situ proximity ligation. Journal of Cellular and Molecular Medicine, 16(7), 1474-1484. https://doi.org/10.1111/j.1582-4934.2011.01436.x

Pinto, R, Carvalho, AS, Conze, T, Magalhães, A, Picco, G, Burchell, JM, Taylor-Papadimitriou, J, Reis, CA, Almeida, R, Mandel, U , Clausen, H, Söderberg, O & David, L 2012, 'Identification of new cancer biomarkers based on aberrant mucin glycoforms by in situ proximity ligation', Journal of Cellular and Molecular Medicine, vol. 16, no. 7, pp. 1474-1484. https://doi.org/10.1111/j.1582-4934.2011.01436.x

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title = "Identification of new cancer biomarkers based on aberrant mucin glycoforms by in situ proximity ligation",

abstract = "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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AU - Pinto, Rita

AU - Carvalho, Ana S

AU - Conze, Tim

AU - Magalhães, Ana

AU - Picco, Gianfranco

AU - Burchell, Joy M

AU - Taylor-Papadimitriou, Joyce

AU - Reis, Celso A

AU - Almeida, Raquel

AU - Mandel, Ulla

AU - Clausen, Henrik

AU - Söderberg, Ola

AU - David, Leonor

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N2 - 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.

AB - 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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DO - 10.1111/j.1582-4934.2011.01436.x

M3 - Journal article

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SN - 1582-1838

VL - 16

SP - 1474

EP - 1484

JO - Journal of Cellular and Molecular Medicine

JF - Journal of Cellular and Molecular Medicine

IS - 7

ER -

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

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