ABO blood group IgM isoagglutinins interact with tumor-associated O-glycan structures in pancreatic cancer
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ABO blood group IgM isoagglutinins interact with tumor-associated O-glycan structures in pancreatic cancer. / Hofmann, Bianca T; Stehr, Anne; Dohrmann, Thorsten; Güngör, Cenap; Herich, Lena; Hiller, Jens; Harder, Sönke; Ewald, Florian; Gebauer, Florian; Tachezy, Michael; Precht, Clarissa; Izbicki, Jakob R; Bockhorn, Maximilian; Wagener, Christoph; Wolters-Eisfeld, Gerrit.
in: CLIN CANCER RES, Jahrgang 20, Nr. 23, 2014, S. 6117-26.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - ABO blood group IgM isoagglutinins interact with tumor-associated O-glycan structures in pancreatic cancer
AU - Hofmann, Bianca T
AU - Stehr, Anne
AU - Dohrmann, Thorsten
AU - Güngör, Cenap
AU - Herich, Lena
AU - Hiller, Jens
AU - Harder, Sönke
AU - Ewald, Florian
AU - Gebauer, Florian
AU - Tachezy, Michael
AU - Precht, Clarissa
AU - Izbicki, Jakob R
AU - Bockhorn, Maximilian
AU - Wagener, Christoph
AU - Wolters-Eisfeld, Gerrit
N1 - ©2014 American Association for Cancer Research.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
U2 - 10.1158/1078-0432.CCR-14-0716
DO - 10.1158/1078-0432.CCR-14-0716
M3 - SCORING: Journal article
C2 - 25320359
VL - 20
SP - 6117
EP - 6126
JO - CLIN CANCER RES
JF - CLIN CANCER RES
SN - 1078-0432
IS - 23
ER -
