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MUC2 mucin is a major carrier of the cancer-associated sialyl-Tn antigen in intestinal metaplasia and gastric carcinomas
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular tools. (Landegren)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular tools. (Landegren)
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2010 (English)In: Glycobiology, ISSN 0959-6658, E-ISSN 1460-2423, Vol. 20, no 2, 199-206 p.Article in journal (Refereed) Published
Abstract [en]

Changes in mucin protein expression and in glycosylation are common features in pre-neoplastic lesions and cancer and are therefore used as cancer-associated markers. De novo expression of intestinal mucin MUC2 and cancer-associated sialyl-Tn antigen are frequently observed in intestinal metaplasia (IM) and gastric cancer. However, despite that these antigens often co-localize, MUC2 has not been demonstrated to be a carrier of sialyl-Tn. By using the in situ proximity ligation assay (in situ PLA), we herein could show that MUC2 is a major carrier of the sialyl-Tn antigen in all IM cases and in most gastric carcinoma cases. The requirement by in situ PLA for the presence of both antigens in close proximity increases the selectivity compared to measurement of co-localization, as determined by immunohistochemistry. Identification of the mucin which is the carrier of a carbohydrate structure offers unique advantages for future development of more accurate diagnostic and prognostic markers.

Place, publisher, year, edition, pages
2010. Vol. 20, no 2, 199-206 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-112103DOI: 10.1093/glycob/cwp161ISI: 000273226500007PubMedID: 19815850OAI: oai:DiVA.org:uu-112103DiVA: diva2:284916
Available from: 2010-01-08 Created: 2010-01-08 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Ligation-mediated Molecular Analysis of Influenza Subtypes, Splicing and Protein Glycosylation
Open this publication in new window or tab >>Ligation-mediated Molecular Analysis of Influenza Subtypes, Splicing and Protein Glycosylation
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Binder-based assays are employed throughout the life sciences. Powerful signal amplification techniques have enabled detection of very rare molecule species diluted in simple buffers. Unspecific binding of primary binders leads to increased background in more complex samples. By requiring two recognition events, ligation-based molecular analyses provide highly specific detection of biomolecules in complex samples.

We developed a highly multiplexed padlock-ligation assay targeting signature sequences in the hemagglutinin and neuraminidase genes. From a panel of 77 avian influenza isolates of all major serotypes, 97% were genotyped correctly in accordance with previous classifications by classical diagnostic methods (Paper I).

Alternative splicing is an important mechanism expanding the proteome. Current analysis techniques fail to provide sequences of complete transcripts beyond the read length of sequencing instruments. We devised and implemented a strategy to compress the sequence information contained in the splicing pattern of a transcript into the presence or absence of sequence-blocks. We demonstrate that this assay yields information about the splicing patterns in thousands of transcripts from cellular cDNA (Paper II).

Expression changes of mucin proteins and glycosylation structures are frequently observed from the early stages of cancer development. Expression of mucin 2 and sialyl-Tn are common features of intestinal metaplasia and gastric cancer, and are known to co-locate. Here we have developed an in situ proximity ligation assay (PLA) directed against mucin 2 and sialyl-Tn. Our study on intestinal metaplasia and gastric cancer tissue sections identified mucin 2 as a major carrier of sialyl-Tn in these conditions, and demonstrated how conveniently glycosylation of proteins can be studied by in situ PLA (Paper III).

This thesis shows how the dual recognition requirement of ligation-based assays can be employed to detect target molecules with high specificity, to analyze several sequence features of nucleic acids or to study the proximity of two antigens in situ.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 39 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 532
Keyword
ligase, proximity ligation, gastric cancer, glycosylation, alternative splicing, avian influenza, padlock probe
National Category
Medical Genetics
Research subject
Molecular Medicine
Identifiers
urn:nbn:se:uu:diva-120016 (URN)978-91-554-7743-1 (ISBN)
Public defence
2010-04-23, Rudbecksalen, Rudbeck Laboratory, Dag Hammarskjölds Väg 20, Uppsala, 09:15 (English)
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Available from: 2010-04-01 Created: 2010-03-04 Last updated: 2010-04-01Bibliographically approved

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Conze, TimLandegren, UlfSöderberg, Ola

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