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.

Cancer-Associated Carbohydrate Antigens as Potential Biomarkers for Hepatocellular Carcinoma

“…Fucosylation of GP73 is reported to be increased in patients with HCC [33]. A previous study suggested that fucosylation plays an important role in the interaction between interleukin-8 and its receptor, thereby inducing the migration of cancer cells in HCC [34]. Our current results suggest that fucosyl GM1 is a candidate hepatic CACAs biomarkers.…”

Clinical significance and biological function of fucosyltransferase 2 in lung adenocarcinoma

“…Accumulating evidences have demonstrated that aberrant glycosylation is the result of alterations in glycosyltransferases that may lead to cancer development and progression [ 9 - 10 ]. Fucosylation, one of the most important types of glycosylation, is regulated by fucosyltransferases (FUTs), which catalyse the transfer of the fucose (Fuc) residue from GDP-fucose donor substrate to acceptor substrates present on oligosaccharides, glycoproteins and glycolipids [ 11 - 13 ]. Deficiency or enhanced expression of FUTs has been reported in various cancers, and associated with cancer progression and metastasis [ 14 - 15 ].…”

“…FUT7 modifies the apoptosis in human hepatocarcinoma cells. FUT8 is upregulated in human hepatoma cell line [ 11 , 14 , 16 - 18 ]. Thus, these results suggest that FUTs may play an important role in cancer progression.…”

Leukocyte-borne α(1,3)-fucose is a negative regulator of β2-integrin-dependent recruitment in lung inflammation

“…In this regard, human neutrophils have 2 neutrophil-bound receptors for the endothelium-bound cytokines CXCR1 and CXCR2, whereas murine neutrophils have only CXCR2 [47]. CXCR2 has been thought to have 2 N-glycan sites [48], to be sensitive to enzymatic deglycosylation, which affects its normal function [49] and has been hypothesized to carry either a(1,2)or a(1,3)-fucose residues [50], which lends credence to our theory that the a(1,3) fucose may affect CXCR2 function. Also, endothelial CXCR2 has been implicated in the regulation of lung endothelial leakiness upon LPS stimulation [28] which may serve to explain why the ratio of Fut4 2/2 Fut7 2/2 :WT cells recovered was higher in the WT recipients (Fig.…”