Accumulation of free complex-type N-glycans in MKN7 and MKN45 stomach cancer cells
Accumulation of free complex-type N-glycans in MKN7 and MKN45 stomach cancer cells
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DOI：
10.1042/bj20071562
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发表时间：
2008-07-15
影响因子：
4.1
通讯作者：
Narimatsu, Hisashi
中科院分区：
文献类型：
--
作者：
Ishizuka, Aya;Hashimto, Yuki;Narimatsu, Hisashi
在N-糖基化反应过程中，已经表明"游离“N-聚糖由脂质连接的寡糖或错误折叠的糖蛋白产生。在这两种情况下，高甘露糖型游离聚糖的出现是有据可查的，并且已经研究了其在胞质溶胶中的分子机制。另一方面，很少，如果有的话，是已知的关于更多的加工，复杂型游离寡糖在哺乳动物细胞的胞质溶胶中的积累。在癌细胞膜组分中N-聚糖的综合分析过程中[纳卡等人（2006）J. Proteome Res.5，8897]，我们发现在胃癌衍生的细胞系MKN 7和MKN 45中积累了大量不寻常的复合型游离N-聚糖。在这些细胞中发现的最丰富和特征性聚糖被确定为NeuAc α 2- 6 Gal β 1-4GlcNAc β 1- 2 Man α 1- 3 Man β 1-4GlcNAc。生化分析表明，由于溶酶体膜的完整性较低，发现的这些聚糖是来自溶酶体的胞质聚糖。由于这些游离N-聚糖的积累仅对所检查的各种癌细胞系中的两种细胞系具有特异性，因此这些胞质N-聚糖可作为诊断特定肿瘤的特异性生物标志物。一个胞质唾液酸酶，Neu 2，被证明参与这些唾液酸聚糖的降解，表明哺乳动物细胞的胞质溶胶可能配备复杂型聚糖的代谢。
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, 8897], we found that a significant amount of unusual, complex-type free N-glycans were accumulated in the stomach cancerderived cell lines, MKN7 and MKN45. The most abundant and characteristic glycan found in these cells was determined to be NeuAc alpha 2-6Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3Man beta 1-4GlcNAc. 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.