title: Fucosylated glycan inhibition of human hepatocellular carcinoma cell migration through binding to chemokine receptors.
abstract: SMMC-7721 hepatocellular carcinoma cells (HCC) were incubated with fucosylated glycoproteins that had been isolated from retinoic acid-treated cells by affinity chromatography. HCC migration was significantly inhibited by AAL- and LCA-glycoproteins. Glycopeptides, obtained by digestion of the glycoproteins with trypsin and papain, were found to have a similar inhibitory effect on HCC migration as the corresponding glycoproteins. The inhibitory actions of the glycoproteins were almost abolished after digestion with alpha-L-1,3/4- or alpha-L-1,2-fucosidase. Induction of HCC migration with chemokines including interleukin-8 (IL-8), lymphotactin, monocyte chemoattractant protein-1, and stroma cell-derived factor-1 was examined and IL-8 was found to be the most potent. Interestingly, the isolated glycoproteins significantly inhibited HCC migration and F-actin aggregation induced by IL-8, whereas the glycans themselves did not induce F-actin assembly. From receptor binding analysis AAL-glycan was found to bind IL-8 receptors especially CXCR2 directly and such binding could be blocked by 3'- or 2'-fucosyllactose. After CXCR2 silence by target RNAi, the cells almost lost the response to AAL-glycan inhibition. Our findings suggest that fucosylation plays an important role in the interaction between IL-8 and its receptors inducing HCC migration.
authors.affiliation: Department of Biochemistry, Shanghai Medical College, Fudan University, Shanghai 200032, People's Republic of China.
authors.forename: Li Hui
authors.initials: LH
authors.lastname: Wu
authors.forename: Bi Zhi
authors.initials: BZ
authors.lastname: Shi
authors.forename: Qian Lei
authors.initials: QL
authors.lastname: Zhao
authors.forename: Xing Zhong
authors.initials: XZ
authors.lastname: Wu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D005643:Fucose / Q000378:metabolism / Q000494:pharmacology*; D006020:Glycopeptides / Q000494:pharmacology; D006023:Glycoproteins / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D019707:Receptors, Chemokine / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D006020:Glycopeptides; D006023:Glycoproteins; D019707:Receptors, Chemokine; D005643:Fucose; D014212:Tretinoin