Comprehensive Clinico-Glycomic Study of 16 Colorectal Cancer Specimens: Elucidation of Aberrant Glycosylation and Its Mechanistic Causes in Colorectal Cancer Cells
Comprehensive Clinico-Glycomic Study of 16 Colorectal Cancer Specimens: Elucidation of Aberrant Glycosylation and Its Mechanistic Causes in Colorectal Cancer Cells
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DOI：
10.1021/pr900092r
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发表时间：
2009-06-01
影响因子：
4.4
通讯作者：
Miyamoto, Yasuhide
中科院分区：
文献类型：
--
作者：
Misonou, Yoshiko;Shida, Kyoko;Miyamoto, Yasuhide
用上皮细胞标记物CD326对正常大肠上皮细胞和结直肠癌细胞的中性和酸性鞘糖脂的结构进行了分析。对16名患者的样本进行了分析。糖鞘糖脂的碳水化合物部分被内糖神经酰胺酶11释放，用吡啶层析标记，并用二维图谱和质谱仪进行鉴定。正常大肠上皮细胞的结构以中性类型1链寡糖的优势表达为特征。在恶变过程中观察到三种特殊的变化：2型寡糖比例增加，α2-3和/或α2-6唾液酸化增加，α1-2岩藻糖基化增加。虽然改变的程度因人而异，但我们发现有两种特征性的改变往往与临床特征有关。其一是从以1型为主的正常大肠上皮细胞转变为以2型为主的结直肠癌细胞。5例有肝转移的患者有此改变。另一种是2例血清CA19-9水平较高的患者a2-3唾液酸特异性升高。对相关G糖基转移酶活性的检查表明，虽然一些变化可以用相关糖基转移酶活性的变化来解释，但另一些则不能。虽然分析的病例数量很少，但这些发现提供了有价值的信息，有助于阐明异常糖基化合成的机制及其与癌症恶性肿瘤的关系。
The structures of neutral and acidic glycosphingolipids from both normal colorectal epithelial cells and colorectal cancer cells, which were highly purified with the epithelial cell marker CD326, have been analyzed. The analysis was performed on samples from 16 patients. The carbohydrate moieties from glycosphingolipids were released by endoglycoceramidase 11, labeled by pyridylamination, and identified using two-dimensional mapping and mass spectrometry. The structures from normal colorectal epithelial cells are characterized by dominant expression of neutral type-1 chain oligosaccharides. Three specific alterations were observed in malignant transformation; increased ratios of type-2 oligosaccharides, increased alpha 2-3 and/or alpha 2-6 sialylation and increased alpha 1-2 fucosylation. Although the degree of alteration varies case to case, we found that two characteristic alterations tend to be associated with clinical features. One is a shift from type-1 dominant normal colorectal epithelial cells to type-2 dominant colorectal cancer cells. This shift was found in 5 patients having hepatic metastasis. The other is specific elevation of a2-3 sialylation observed in 2 cases exhibiting high serum levels of CA 19-9. Examination of the activities of the related g glycosyltransferases revealed that while some alterations could be accounted for by changes in the activities of related glycosyltransferases others could not. Although the number of cases analyzed is small, these findings provide valuable information which will help in the elucidation of the mechanism of synthesis of aberrant glycosylation and its involvement in cancer malignancy.