Insights into glycan biosynthesis in chemically-induced hepatocellular carcinoma in rats: A glycomic analysis  

作　　者：Amr Amin Asma Bashir Nazar Zaki Diane McCarthy Sanjida Ahmed Mohamed Lotfy 

机构地区：[1]Department of Biology,College of Science,UAE University [2]Zoology Department,Faculty of Science,Cairo University [3]Intelligent Systems,College of Information Technology,UAE University [4]Ezose Sciences Inc.,Pine Brook [5]Eastern Biotech and Life Sciences [6]Hormones Department,National Research Center

出　　处：《World Journal of Gastroenterology》2015年第20期6167-6179,共13页世界胃肠病学杂志（英文版）

基　　金：Supported by National Research Foundation Grant No.UIRCA 2012-21832 for A.Amin

摘　　要：AIM： To evaluate the qualitative and quantitativechanges in N-linked glycosylation, which occurredin association with diethyl nitrosamine-inducedhepatocellular carcinoma （HCC） in rodents.METHODS： Liver tissues of （1） normal （non-tumorbearing）rats; and （2） tumor-bearing rats; were collectedand were used for histological and GlycanMap？ analyses.Briefly, GlycanMap？ analysis is a high-throughputassay that provides a structural and quantitativereadout of protein-associated glycans using a unique,automated 96-well assay technology coupled tomatrix-assisted laser desorption/ionization time-offlightmass spectrometry and custom bioinformatics.Histopathological studies were carried out to ensure thedevelopment of HCC in the tested animals.RESULTS： The N-glycomic analysis revealed 5glycans; Glc1Man9GlcNAc2, Gal2Man3GlcNac4Fuc1Neu1,Man4G l c N a c 2, G a l 2Man3G l c N a c 4Neu3OAc 3, andMan3GlcNac5Fuc1, which showed significant changesin rat HCC tissues when compared with normal livertissues. Four glycans were increased （P 〈 0.05） andGlc1Man9GlcNAc2 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 wasobserved compared to normal rats. Importantly, HCCrats showed an increase （P 〈 0.05） in both tumorassociatedcarbohydrates and in branched glycans. Thechanges in glycans correlated well with glycan flowchanges reported in the glycan biosynthetic pathway,which indicates the importance of enzyme activitiesinvolved in glycan synthesis at different subcellularlocalizations.CONCLUSION： The reported HCC-associated changesin glycan flow and subcellular localization explain theincrease in high mannose glycans and siayl Lewisglycans common in HCC liver tissues.AIM:To evaluate the qualitative and quantitative changes in N-linked glycosylation,which occurred in association with diethyl nitrosamine-induced hepatocellular carcinoma(HCC) in rodents.METHODS:Liver tissues of(1) normal(non-tumorbearing) 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-offlight mass spectrometry and custom bioinformatics.Histopathological studies were carried out to ensure the development of HCC in the tested animals.RESULTS:The N-glycomic analysis revealed 5glycans;Glc1Man9GlcNAc2,Gal2Man3GlcNac4Fuc1Neu1,Man4GlcNac2,Gal2Man3GlcNac4Neu3OAc3,and Man3GlcNac5Fuc1,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 tumorassociated 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.CONCLUSION: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.

关 键 词：Matrix-assisted laser desorption/ionizationtime-of-flight mass SPECTROMETRY Hepatocellularcarcinoma GLYCOMICS Biosynthetic pathways 

分 类 号：R735.7[医药卫生—肿瘤]