Amin Amr, Bashir Asma, Zaki Nazar, McCarthy Diane, Ahmed Sanjida, Lotfy Mohamed
Amr Amin, Asma Bashir, Mohamed Lotfy, Department of Biology, College of Science, UAE University, Al-Ain 15551, United Arab Emirates.
World J Gastroenterol. 2015 May 28;21(20):6167-79. doi: 10.3748/wjg.v21.i20.6167.
To evaluate the qualitative and quantitative changes in N-linked glycosylation, which occurred in association with diethyl nitrosamine-induced hepatocellular carcinoma (HCC) in rodents.
Liver tissues of (1) normal (non-tumor-bearing) rats; and (2) tumor-bearing rats; were collected and were used for histological and GlycanMap analyses. Briefly, GlycanMap analysis is a high-throughput assay that provides a structural and quantitative readout of protein-associated glycans using a unique, automated 96-well assay technology coupled to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and custom bioinformatics. Histopathological studies were carried out to ensure the development of HCC in the tested animals.
The N-glycomic analysis revealed 5 glycans; Glc₁Man₉GlcNAc₂, Gal₂Man₃GlcNac₄Fuc₁Neu₁, Man₄GlcNac₂, Gal₂Man₃GlcNac₄Neu₃OAc₃, and Man₃GlcNac₅ Fuc₁, which showed significant changes in rat HCC tissues when compared with normal liver tissues. Four glycans were increased (P < 0.05) and Glc₁Man₉GlcNAc₂ was decreased (5.89 ± 0.45 vs 3.54 ± 0.21, P < 0.01) in HCC tissues compared to normal liver tissues. An increase (66.5 ± 1.05 vs 62.7 ± 1.1, P < 0.05) in high-mannose structures in HCC rats was observed compared to normal rats. Importantly, HCC rats showed an increase (P < 0.05) in both tumor-associated carbohydrates and in branched glycans. The changes in glycans correlated well with glycan flow changes reported in the glycan biosynthetic pathway, which indicates the importance of enzyme activities involved in glycan synthesis at different subcellular localizations.
The reported HCC-associated changes in glycan flow and subcellular localization explain the increase in high mannose glycans and siayl Lewis glycans common in HCC liver tissues.
评估与二乙基亚硝胺诱导的啮齿动物肝细胞癌（HCC）相关的N-连接糖基化的定性和定量变化。
收集（1）正常（无肿瘤）大鼠和（2）荷瘤大鼠的肝脏组织，用于组织学和聚糖图谱分析。简要地说，聚糖图谱分析是一种高通量检测方法，它使用独特的自动化96孔检测技术，结合基质辅助激光解吸/电离飞行时间质谱和定制生物信息学，提供与蛋白质相关聚糖的结构和定量读数。进行组织病理学研究以确保受试动物发生HCC。
N-糖组分析揭示了5种聚糖；Glc₁Man₉GlcNAc₂、Gal₂Man₃GlcNac₄Fuc₁Neu₁、Man₄GlcNac₂、Gal₂Man₃GlcNac₄Neu₃OAc₃和Man₃GlcNac₅ Fuc₁，与正常肝组织相比，这些聚糖在大鼠HCC组织中显示出显著变化。与正常肝组织相比，HCC组织中有4种聚糖增加（P < 0.05），而Glc₁Man₉GlcNAc₂减少（5.89 ± 0.45对3.54 ± 0.21，P < 0.01）。与正常大鼠相比，观察到HCC大鼠中高甘露糖结构增加（66.5 ± 1.05对62.7 ± 1.1，P < 0.05）。重要的是，HCC大鼠的肿瘤相关碳水化合物和分支聚糖均增加（P < 0.05）。聚糖的变化与聚糖生物合成途径中报道的聚糖流变化密切相关，这表明参与不同亚细胞定位聚糖合成的酶活性的重要性。
报道的与HCC相关的聚糖流和亚细胞定位变化解释了HCC肝组织中常见的高甘露糖聚糖和唾液酸化路易斯聚糖的增加。
