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Accumulation of free Neu5Ac-containing complex-type N-glycans in human pancreatic cancers

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Abstract

We have analyzed the structures of glycosphingolipids and intracellular free glycans in human cancers. In our previous study, trace amounts of free N-acetylneuraminic acid (Neu5Ac)-containing complex-type N-glycans with a single GlcNAc at each reducing terminus (Gn1 type) was found to accumulate intracellularly in colorectal cancers, but were undetectable in most normal colorectal epithelial cells. Here, we used cancer glycomic analyses to reveal that substantial amounts of free Neu5Ac-containing complex-type N-glycans, almost all of which were α2,6-Neu5Ac-linked, accumulated in the pancreatic cancer cells from three out of five patients, but were undetectable in normal pancreatic cells from all five cases. These molecular species were mostly composed of five kinds of glycans having a sequence Neu5Ac-Gal-GlcNAc-Man-Man-GlcNAc and one with the following sequence Neu5Ac-Gal-GlcNAc-Man-(Man-)Man-GlcNAc. The most abundant glycan was Neu5Acα2-6Galβ1-4GlcNAcβ1-2Manα1-3Manβ1-4GlcNAc, followed by Neu5Acα2-6Galβ1-4GlcNAcβ1-2Manα1-6Manβ1-4GlcNAc. This is the first study to show unequivocal evidence for the occurrence of free Neu5Ac-linked N-glycans in human cancer tissues. Our findings suggest that free Neu5Ac-linked glycans may serve as a useful tumor marker.

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Abbreviations

Neu5Ac:

N-acetylneuraminic acid

SGP:

Sialylglycopeptide

Cer:

Ceramide

GM3:

Neu5Acα3Galβ4GlcCer

LST-c:

Neu5Acα6Galβ4GlcNAcβ3Galβ4GlcCer

GM1:

Galβ3GalNAcβ4(Neu5Acα3)Galβ4GlcCer

LST-a:

Neu5Acα3Galβ3GlcNAcβ3Galβ4GlcCer

Disialyl Lc4 :

Neu5Acα3Galβ3(Neu5Acα6)GlcNAcβ3Galβ4GlcCer

SSEA-4:

Neu5Acα3Galβ3GalNAcβ3Galα4Galβ4GlcCer

Disialyl SSEA-3:

Neu5Acα3Galβ3(Neu5Acα6)GalNAcβ3Galα4Galβ4GlcCer

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Acknowledgements

This work was supported in part by the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO). This study was performed in part as a research program of the Project for Development of Innovative Research on Cancer Therapeutics (P-Direct), Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Correspondence to Yasuhide Miyamoto.

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Yabu, M., Korekane, H., Takahashi, H. et al. Accumulation of free Neu5Ac-containing complex-type N-glycans in human pancreatic cancers. Glycoconj J 30, 247–256 (2013). https://doi.org/10.1007/s10719-012-9435-9

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  • DOI: https://doi.org/10.1007/s10719-012-9435-9

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