During the N-glycosylation reaction, it has been shown that ‘free’ N-glycans are generated either from lipid-linked oligosaccharides or from misfolded glycoproteins. In both cases, occurrence of high mannose-type free glycans is well-documented, and the molecular mechanism for their catabolism in the cytosol has been studied. On the other hand, little, if anything, is known with regard to the accumulation of more processed, complex-type free oligosaccharides in the cytosol of mammalian cells. During the course of comprehensive analysis of N-glycans in cancer cell membrane fractions [Naka et al. (2006) J. Proteome Res. 5, 88–97], we found that a significant amount of unusual, complex-type free N-glycans were accumulated in the stomach cancer-derived cell lines, MKN7 and MKN45. The most abundant and characteristic glycan found in these cells was determined to be NeuAcα2-6Galβ1-4GlcNAcβ1-2Manα1-3Manβ1-4GlcNAc. Biochemical analyses indicated that those glycans found were cytosolic glycans derived from lysosomes due to low integrity of the lysosomal membrane. Since the accumulation of these free N-glycans was specific to only two cell lines among the various cancer cell lines examined, these cytosolic N-glycans may serve as a specific biomarker for diagnosis of specific tumours. A cytosolic sialidase, Neu2, was shown to be involved in the degradation of these sialoglycans, indicating that the cytosol of mammalian cells might be equipped for metabolism of complex-type glycans.
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Research Article|
June 26 2008
Accumulation of free complex-type N-glycans in MKN7 and MKN45 stomach cancer cells
Aya Ishizuka;
Aya Ishizuka
*School of Pharmacy, Kinki University, Kowakae 3-4-1, Higashi-Osaka, Osaka 577-8502, Japan
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Yuki Hashimto;
Yuki Hashimto
*School of Pharmacy, Kinki University, Kowakae 3-4-1, Higashi-Osaka, Osaka 577-8502, Japan
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Ryosuke Naka;
Ryosuke Naka
*School of Pharmacy, Kinki University, Kowakae 3-4-1, Higashi-Osaka, Osaka 577-8502, Japan
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Mitsuhiro Kinoshita;
Mitsuhiro Kinoshita
*School of Pharmacy, Kinki University, Kowakae 3-4-1, Higashi-Osaka, Osaka 577-8502, Japan
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Kazuaki Kakehi;
Kazuaki Kakehi
1
*School of Pharmacy, Kinki University, Kowakae 3-4-1, Higashi-Osaka, Osaka 577-8502, Japan
1Correspondence may be addressed to either of these authors (email k_kakehi@phar.kindai.ac.jp or tsuzuki_gm@riken.jp).
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Junichi Seino;
Junichi Seino
†Glycometabolome Laboratory, Frontier Research System, RIKEN (The Institute for Physical and Chemical Research); 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
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Yoko Funakoshi;
Yoko Funakoshi
†Glycometabolome Laboratory, Frontier Research System, RIKEN (The Institute for Physical and Chemical Research); 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
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Tadashi Suzuki;
Tadashi Suzuki
1
†Glycometabolome Laboratory, Frontier Research System, RIKEN (The Institute for Physical and Chemical Research); 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
‡CREST (Core Research for Evolutionary Science and Technology), JST (Japan Science and Technology Agency), Saitama, Japan
1Correspondence may be addressed to either of these authors (email k_kakehi@phar.kindai.ac.jp or tsuzuki_gm@riken.jp).
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Akihiko Kameyama;
Akihiko Kameyama
§Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology (AIST), Open Space Laboratory C-2, 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568, Japan
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Hisashi Narimatsu
Hisashi Narimatsu
§Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology (AIST), Open Space Laboratory C-2, 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568, Japan
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Publisher: Portland Press Ltd
Received:
November 16 2007
Revision Received:
April 01 2008
Accepted:
April 09 2008
Accepted Manuscript online:
April 09 2008
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biochem J (2008) 413 (2): 227–237.
Article history
Received:
November 16 2007
Revision Received:
April 01 2008
Accepted:
April 09 2008
Accepted Manuscript online:
April 09 2008
Citation
Aya Ishizuka, Yuki Hashimto, Ryosuke Naka, Mitsuhiro Kinoshita, Kazuaki Kakehi, Junichi Seino, Yoko Funakoshi, Tadashi Suzuki, Akihiko Kameyama, Hisashi Narimatsu; Accumulation of free complex-type N-glycans in MKN7 and MKN45 stomach cancer cells. Biochem J 15 July 2008; 413 (2): 227–237. doi: https://doi.org/10.1042/BJ20071562
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