Department of Immunology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamichi, Higashinari-ku, Osaka, Japan.
Glycoconj J. 2013 Apr;30(3):247-56. doi: 10.1007/s10719-012-9435-9. Epub 2012 Aug 14.
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.
我们分析了人类癌症中的糖脂和细胞内游离糖的结构。在我们之前的研究中，在结直肠癌细胞内发现了痕量的含有单个 GlcNAc 的末端还原的游离 N-乙酰神经氨酸 (Neu5Ac)- 含有复合型 N-聚糖 (Gn1 型)，但在大多数正常结直肠上皮细胞中无法检测到。在这里，我们使用癌症糖组学分析来揭示，大量的含有游离 Neu5Ac 的复合型 N-聚糖，几乎全部都是α2,6-Neu5Ac 连接的，在来自五名患者中的三名胰腺癌细胞中积累，但在来自所有五名正常胰腺细胞中无法检测到。这些分子种类主要由五种糖组成，序列为 Neu5Ac-Gal-GlcNAc-Man-Man-GlcNAc，一种序列为 Neu5Ac-Gal-GlcNAc-Man-(Man-)Man-GlcNAc。最丰富的聚糖是 Neu5Acα2-6Galβ1-4GlcNAcβ1-2Manα1-3Manβ1-4GlcNAc，其次是 Neu5Acα2-6Galβ1-4GlcNAcβ1-2Manα1-6Manβ1-4GlcNAc。这是首次明确证明人类癌症组织中存在游离 Neu5Ac 连接的 N-聚糖的研究。我们的发现表明，游离 Neu5Ac 连接的聚糖可能作为一种有用的肿瘤标志物。
