Fucosylated glycan inhibition of human hepatocellular carcinoma cell migration through binding to chemokine receptors.
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.
Wu
Li Hui
LH
Department of Biochemistry, Shanghai Medical College, Fudan University, Shanghai 200032, People's Republic of China.
Shi
Bi Zhi
BZ
Zhao
Qian Lei
QL
Wu
Xing Zhong
XZ
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
D006020:Glycopeptides; D006023:Glycoproteins; D019707:Receptors, Chemokine; D005643:Fucose; D014212:Tretinoin