Universität zu Köln

Hofmann, Bianca T., Stehr, Anne, Dohrmann, Thorsten, Guengoer, Cenap, Herich, Lena, Hiller, Jens, Harder, Soenke, Ewald, Florian, Gebauer, Florian, Tachezy, Michael, Precht, Clarissa, Izbicki, Jakob R., Bockhorn, Maximilian, Wagener, Christoph and Wolters-Eisfeld, Gerrit ORCID: 0000-0002-2984-6515 (2014). ABO Blood Group IgM Isoagglutinins Interact with Tumor-Associated O-Glycan Structures in Pancreatic Cancer. Clin. Cancer Res., 20 (23). S. 6117 - 6127. PHILADELPHIA: AMER ASSOC CANCER RESEARCH. ISSN 1557-3265

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Abstract

Purpose: The ABO gene locus is associated with the risk of developing pancreatic ductal adenocarcinoma (PDAC) resulting in an increased incidence in individuals with non-O blood groups. Up to 90% of PDAC specimens display alterations in mucin type O-GalNAc glycosylation. Because aberrant O-GalNAc glycans (Tn and T antigen) are structurally related to blood group A and B glycans, we investigated the role of IgM isoagglutinins in PDAC. Experimental Design: Binding studies of IgM isoagglutinins toward blood group A, B, Tn antigen, and T antigen glycoconjugates from patients with PDAC and healthy individuals were conducted. Isoagglutinin titers and total IgM were compared between patients with PDAC and control group. An anti-A antibody was used for immunoprecipitation of aberrant O-glycosylated tumor proteins and subsequent mass spectromic analysis. Results: We found that IgM isoagglutinins bind blood group antigens, Tn and T glycoconjugates as well as tumor-derived glycoproteins. Blood group A isoagglutinins exhibited a strong binding toward blood group B antigen and T antigen, whereas blood group B showed binding to blood group A antigen and Tn antigen. Furthermore, we confirmed a decreased frequency in individuals with blood group O and observed a significant decrease of IgM isoagglutinin titers in PDAC sera compared with control sera, whereas total IgM levels were unaltered. We identified new PDAC-derived O-GalNAc glycoproteins by mass spectrometry using a blood group A-specific antibody. Conclusion: Our data elucidated a novel interaction of blood group IgM isoagglutinins and PDAC O-GalNAc glycoproteins that may contribute to the pathogenesis and progression of pancreatic cancer. (C) 2014 AACR.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hofmann, Bianca T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stehr, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Dohrmann, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Guengoer, Cenap UNSPECIFIED UNSPECIFIED UNSPECIFIED Herich, Lena UNSPECIFIED UNSPECIFIED UNSPECIFIED Hiller, Jens UNSPECIFIED UNSPECIFIED UNSPECIFIED Harder, Soenke UNSPECIFIED UNSPECIFIED UNSPECIFIED Ewald, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Gebauer, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Tachezy, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Precht, Clarissa UNSPECIFIED UNSPECIFIED UNSPECIFIED Izbicki, Jakob R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bockhorn, Maximilian UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagener, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolters-Eisfeld, Gerrit UNSPECIFIED orcid.org/0000-0002-2984-6515 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-421440
DOI:	10.1158/1078-0432.CCR-14-0716
Journal or Publication Title:	Clin. Cancer Res.
Volume:	20
Number:	23
Page Range:	S. 6117 - 6127
Date:	2014
Publisher:	AMER ASSOC CANCER RESEARCH
Place of Publication:	PHILADELPHIA
ISSN:	1557-3265
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HUMAN TRANSFERRIN RECEPTOR; GROUP-RELATED ANTIGENS; SIALYL-TN; BREAST-CANCER; EXPRESSION; GLYCOSYLATION; GLYCOPROTEOME; MUTATIONS; BINDING; SYSTEM Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42144