Osaka University Graduate School of Medicine, Department of Molecular Biochemistry and Clinical Investigation, 1-7 Yamada-oka, Suita 565-0871, Japan.
Biomolecules. 2012 Jan 30;2(1):34-45. doi: 10.3390/biom2010034.
Oligosaccharides, sequences of carbohydrates conjugated to proteins and lipids, are arguably the most abundant and structurally diverse class of molecules. Fucosylation is one of the most important oligosaccharide modifications involved in cancer and inflammation. Recent advances in glycomics have identified several types of glyco-biomarkers containing fucosylation that are linked to certain types of cancer. Fucosylated alpha-fetoprotein (AFP) is widely used in the diagnosis of hepatocellular carcinoma because it is more specific than alpha-fetoprotein. High levels of fucosylated haptoglobin have also been found in sera of patients with various carcinomas. We have recently established a simple lectin-antibody ELISA to measure fucosylated haptoglobin and to investigate its clinical use. Cellular fucosylation is dependent upon fucosyltransferase activity and the level of its donor substrate, guanosine diphosphate (GDP)-fucose. GDP-mannose-4,6-dehydratase (GMDS) is a key enzyme involved in the synthesis of GDP-fucose. Mutations of GMDS found in colon cancer cells induced a malignant phenotype, leading to rapid growth in athymic mice resistant to natural killer cells. This review describes the role of fucosylated haptoglobin as a cancer biomarker, and discusses the possible biological role of fucosylation in cancer development.
寡糖是与蛋白质和脂质结合的碳水化合物序列，可以说是最丰富和结构最多样化的一类分子。糖基化是癌症和炎症中涉及的最重要的寡糖修饰之一。糖组学的最新进展已经确定了几种含有岩藻糖基化的糖基生物标志物，这些标志物与某些类型的癌症有关。岩藻糖基化甲胎蛋白（AFP）在肝癌的诊断中被广泛应用，因为它比甲胎蛋白更具特异性。在各种癌症患者的血清中也发现了高水平的岩藻糖化触珠蛋白。我们最近建立了一种简单的凝集素-抗体 ELISA 来测量岩藻糖化触珠蛋白，并研究其临床应用。细胞岩藻糖化依赖于岩藻糖基转移酶活性及其供体底物 GDP-岩藻糖的水平。GDP-甘露糖-4,6-脱水酶（GMDS）是合成 GDP-岩藻糖的关键酶。在结肠癌细胞中发现的 GMDS 突变诱导了恶性表型，导致在对自然杀伤细胞有抗性的无胸腺小鼠中快速生长。本文综述了岩藻糖化触珠蛋白作为癌症生物标志物的作用，并讨论了糖基化在癌症发展中的可能生物学作用。
