Journal Article

PreJuSER-49189

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The ST6GalNAc-l sialyltransferase localises throughout the Golgi and is responsible for the synthesis of the tumour associated sialyl Tn O-glycan in human breast cancer

Sewell, R. ; Bäckstrom, M. ; Dalziel, M. ; Gschmeissner, S. ; Karlsson, H. ; Noll, T.FZJ* ; Gätgens, J.FZJ* ; Clausen, H. ; Hansson, G. ; Burchell, J. ; Taylor-Papadimitriou, J.

2006
Soc. Bethesda, Md.

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Please use a persistent id in citations: http://hdl.handle.net/2128/2839  doi:10.1074/jbc.M511826200

Abstract: The functional properties of glycoproteins are strongly influenced by their profile of glycosylation, and changes in this profile are seen in malignancy. In mucin-type O-linked glycosylation these changes can result in the production of mucins such as MUC1, carrying shorter sialylated O-glycans, and with different site occupancy. Of the tumor-associated sialylated O-glycans, the disaccharide, sialyl-Tn (sialic acid alpha2,6GalNAc), is expressed by 30% of breast carcinomas and is the most tumor-specific. The ST6GalNAc-I glycosyltransferase, which can catalyze the transfer of sialic acid to GalNAc, shows a highly restricted pattern of expression in normal adult tissues, being largely limited to the gastrointestinal tract and absent in mammary gland. In breast carcinomas, however, a complete correlation between the expression of RNA-encoding ST6GalNAc-I and the expression of sialyl-Tn is evident, demonstrating that the expression of sialyl-Tn results from switching on expression of hST6GalNAc-I. Endogenous or exogenous expression of hST6GalNAc-I (but not ST6GalNAc-II) always results in the expression of sialyl-Tn. This ability to override core 1/core 2 pathways of O- linked glycosylation is explained by the localization of ST6GalNAc-I, which is found throughout the Golgi stacks. The development of a Chinese hamster ovary (CHO) cell line expressing MUC1 and ST6GalNAc-I allowed the large scale production of MUC1 carrying 83% sialyl-Tn O-glycans. The presence of ST6GalNAc-I in the CHO cells reduced the number of O-glycosylation sites occupied in MUC1, from an average of 4.3 to 3.8 per tandem repeat. The availability of large quantities of this MUC1 glycoform will allow the evaluation of its efficacy as an immunogen for immunotherapy of MUC1/STn-expressing tumors.

Keyword(s): Animals (MeSH) ; Antigens, Neoplasm: chemistry (MeSH) ; Antigens, Tumor-Associated, Carbohydrate: chemistry (MeSH) ; Blotting, Northern (MeSH) ; Blotting, Western (MeSH) ; Breast Neoplasms: enzymology (MeSH) ; Breast Neoplasms: pathology (MeSH) ; CHO Cells (MeSH) ; Cell Line, Tumor (MeSH) ; Chromatography, Liquid (MeSH) ; Cloning, Molecular (MeSH) ; Cricetinae (MeSH) ; Female (MeSH) ; Flow Cytometry (MeSH) ; Glycosylation (MeSH) ; Golgi Apparatus: enzymology (MeSH) ; Golgi Apparatus: metabolism (MeSH) ; Humans (MeSH) ; Immunotherapy: methods (MeSH) ; K562 Cells (MeSH) ; Mammary Glands, Human: metabolism (MeSH) ; Microscopy, Fluorescence (MeSH) ; Microscopy, Immunoelectron (MeSH) ; Models, Chemical (MeSH) ; Polysaccharides: chemistry (MeSH) ; Polysaccharides: metabolism (MeSH) ; Recombinant Fusion Proteins: chemistry (MeSH) ; Reverse Transcriptase Polymerase Chain Reaction (MeSH) ; Sialyltransferases: chemistry (MeSH) ; Sialyltransferases: metabolism (MeSH) ; Spectrometry, Mass, Electrospray Ionization (MeSH) ; Transfection (MeSH) ; Antigens, Neoplasm ; Antigens, Tumor-Associated, Carbohydrate ; Polysaccharides ; Recombinant Fusion Proteins ; sialosyl-Tn antigen ; Sialyltransferases ; CMP-N-acetylneuraminate-alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase

Note: Record converted from VDB: 12.11.2012

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Contributing Institute(s):

1. Biotechnologie 2 (IBT-2)

Research Program(s):

1. Biotechnologie (PBT)

Appears in the scientific report 2006

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Database coverage:

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