title: Enhanced expression of α2,3-linked sialic acids promotes gastric cancer cell metastasis and correlates with poor prognosis.
abstract: Gastric cancer (GC) is a highly metastatic disease and one of the leading causes of cancer death in the world. Aberrant glycosylation is one of many molecular changes that accompany malignant transformation. This study was aimed at identification of glycan profiling changes in GC progression and its potential mechanisms. We employed a microarray with 91 lectins to compare the differential glycans in the three human GC cell lines, SGC-7901, BGC-823 and MGC-803. According to glycan-binding specificities of lectins, all GC cell lines expressed common sugar structures, such as mannose, galactose and fucose. Importantly, we found that the binding of Maackia amurensis lectin-I (MAL-I) to GC cells was proportional to their metastatic capacity. Further analysis revealed that the level of α2,3-linked sialic acids (α2-3Sia), which can be recognized by MAL-I, was significantly overexpressed in MGC-803 cells, while low expression was detected in SGC-7901 cells. In addition, the mRNA and protein expression levels of β-galactoside α2,3-sialyltransferase IV (ST3Gal-IV), which was related to the synthesis of α2-3Sia, were substantially increased in MGC-803 cells. Knockdown of ST3Gal-IV in MGC-803 cells led to a decreased level of α2-3Sia and decreased ability of invasion and migration. Exogenous expression of ST3Gal-IV in SGC-7901 cells enhanced cell migration, invasion and the content of α2-3Sia. Furthermore, the staining of MAL-I in GC tissues showed that high expression of α2-3Sia was closely correlated with lymph node metastasis, TNM stage and poor overall survival. These findings lead to better understanding of the function of α2-3Sia in the progression and metastasis of GC. This property may be important for developing new therapeutic approaches for GC.
authors.affiliation: Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Center for Evidence-based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Junbo
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Luo
authors.affiliation: Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ke
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Dong
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D005260:Female; D005697:Galactosides / Q000378:metabolism; D006031:Glycosylation; D006601:Hexoses / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D008207:Lymphatic Metastasis; D029901:Maackia / Q000737:chemistry; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009367:Neoplasm Staging; D011134:Polysaccharides / Q000378:metabolism; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D012794:Sialic Acids / Q000096:biosynthesis*; D012799:Sialyltransferases / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
chemical_list: D014408:Biomarkers, Tumor; D005697:Galactosides; D006601:Hexoses; D037102:Lectins; D011134:Polysaccharides; D012333:RNA, Messenger; D012794:Sialic Acids; C007816:beta-galactoside; D012799:Sialyltransferases; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase