title: Accumulation of free complex-type N-glycans in MKN7 and MKN45 stomach cancer cells.
abstract: 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 NeuAcalpha2-6Galbeta1-4GlcNAcbeta1-2Manalpha1-3Manbeta1-4GlcNAc. 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.
authors.affiliation: School of Pharmacy, Kinki University, Kowakae 3-4-1, Higashi-Osaka, Osaka 577-8502, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Ishizuka
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hashimto
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Naka
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Kakehi
authors.forename: Junichi
authors.initials: J
authors.lastname: Seino
authors.forename: Yoko
authors.initials: Y
authors.lastname: Funakoshi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kameyama
authors.forename: Hisashi
authors.initials: H
authors.lastname: Narimatsu
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002845:Chromatography / Q000379:methods; D003600:Cytosol / Q000378:metabolism; D019075:Electrophoresis, Capillary; D005786:Gene Expression Regulation; D006031:Glycosylation; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008954:Models, Biological; D019158:N-Acetylneuraminic Acid / Q000737:chemistry; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism; D011134:Polysaccharides / Q000737:chemistry* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D009844:Oligosaccharides; D011134:Polysaccharides; D019158:N-Acetylneuraminic Acid