title: The role of anti-LeY antibody in the downregulation of MAPKs/COX-2 pathway in gastric cancer.
abstract: Monoclonal antibody-based treatments of cancer which serve as magic 'bullets' have been established as one of the most successful therapeutic strategies. A variety of antigens has been investigated as targets for the mAb therapy of gastric cancer, including the carbohydrate type 2 blood group antigen. Lewis Y (LeY) is overexpressed on tumor cells surface either as glycoproteins or glycolipids. LeY is difucosylated oligosaccharide with the chemical structure [Fucα1,2Galβ1→4(Fucα1,3)GlcNAcβ1→R], which is catalyzed by fucosyltransferases, such as FUT1 (α1,2) and FUT4 (α1,3). The role of LeY antigen in cancer treatment and prevention has been extensively studied. Moreover, the cyclooxygenase- 2 (COX-2) is an early event protein, highly expressed in H. pylori-related gastric cancer. COX-2 may play a pivotal part in the maintenance of tumor viability, growth, and metastasis. The COX-2 is upregulated in a variety of cancers, including gastric cancer. However, its inhibition may prevent or reverse gastric carcinogenesis. H. pylori mediated alteration of COX-2 through MAPKs pathway is one of the mechanisms that is implicated in gastric cancer. We have found COX-2 and LeY to be correlative sources of specific gastric biomarkers in gastric cancer, which is upregulated in the gastric cancer through MAPKs pathway. In addition, the anti-LeY antibody significantly downregulated the COX-2 expression through MAPKs pathway, helpful to the treatment of gastric cancer. In this review, we summarize the therapeutic effect of anti-LeY antibody, including the crucial role of COX-2 and LeY antigen in gastric cancer and discuss the COX-2 inhibition by anti-LeY antibody through MAPKs pathway.
authors.forename: Faisal
authors.initials: F
authors.lastname: Aziz
authors.affiliation: Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian, P.R. China. yanqiu63@126.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qiu
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D006031:Glycosylation / Q000187:drug effects; D016480:Helicobacter pylori / Q000187:drug effects; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D007983:Lewis Blood Group Antigens; C094162:Lewis Y antigen; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human