Abstract
The object of the study is to identify N-glycan profiling changes associated with gastric cancer and explore the impact of core-fucosylation on biological behaviors of human gastric cancer cells. A total of 244 subjects including gastric cancer, gastric ulcer and healthy control were recruited. N-glycan profiling from serum and total proteins in gastric tissues was analyzed by DNA sequencer-assisted fluorophore-assisted capillary electrophoresis. The abundance of total core-fucosylated residues and the expression of enzymes involved in core-fucosylation were analyzed with lectin blot, quantitative reverse transcription-polymerase chain reaction, western blot, Immunohistochemical staining and lectin-histochemical staining. The recombinant plasmids of GDP-fucose transporter and α-1,6-fucosyltransferase (Fut8) were constructed and transfected into gastric cancer cell lines BGC-823 and SGC-7901. CCK-8 and wound healing assay were used to assess the functional impact of core-fucosylation modulation on cell proliferation and migration. Characteristic serum N-glycan profiles were found in gastric cancer. Compared with the healthy control, a trianntenary structure abundance, peak 9 (NA3Fb), was increased significantly in gastric cancer, while the total abundance of core-fucosylated residues (sumfuc) was decreased. Core-fucosylated structures, peak6(NA2F) and peak7(NA2FB) were deceased in gastric tumor tissues when compared with that in adjacent non-tumor tissues. Consistently, lens culinaris agglutinin (LCA)-binding proteins were decreased significantly in sera of gastric cancer, and protein level of Fut8 was decreased significantly in gastric tumor tissues compared with that in adjacent non-tumor tissues. Upregulation of GDP-Tr and Fut8 could inhibit proliferation, but had no significant influence on migration of BGC-823 and SGC-7901 cells. Core-fucosylation is down regulated in gastric cancer. Upregulation of core-fucosylation could inhibit proliferation of the human gastric cancer cells.
Highlights
The gastric cancer (GC) is the fourth most common cancer and the second most common cause of cancer related death worldwide [1,2,3], prevalent in many Asian countries, especially China[4]
We have identified some N-glycan markers in heptatocellular carcinoma (HCC) and colon cancer using a capillary based electrophoresis called DNA sequencer-assisted fluorophore-assisted capillary electrophoresis (DSA-FACE) [11]
Comparison of sumfuc between gastric cancer and other digestive system cancers Previously we have studied the N-Glycan profiling of hepatocellular carcinoma (HCC) [19] and colorectal cancer (CRC) [20]
Summary
The gastric cancer (GC) is the fourth most common cancer and the second most common cause of cancer related death worldwide [1,2,3], prevalent in many Asian countries, especially China[4]. Upon in-depth characterization of N-linked glycoproteins and disease-associated glycosylation changes, several methodologies have been developed. It has been reported that a-1, 6-fucosyltransferase (Fut8) activity and expression is increased in several human cancers, suggesting a role for this enzyme in tumor development and progression, such as HCC [12], colorectal cancer [13], nonsmall cell lung cancer [14] and ovarian serous adenocarcinoma [15]. Altered core-fucosylation is one of the most important abnormal glycosylated modification identified in malignancies. Fut catalyzes the transfer of fucose from guanosine diphosphate (GDP)-fucose to the innermost GlcNAc of hybrid and complex N-linked oligosaccharides via an a-1,6-linkage, resulting in core-fucosylated glycoproteins [16,17] and altering biological function of resulting glycoproteins [18]. Many studies have reported the association between altered core-fucosylation and other aggressive tumors, to our knowledge, the influence of core-fucosylation on gastric cancer remains unknown.
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