Title:The Role of Anti-LeY Antibody in the Downregulation of MAPKs/COX-2 Pathway in Gastric Cancer
VOLUME: 15 ISSUE: 4
Author(s):Faisal Aziz and Yan Qiu
Affiliation:Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian, P.R. China.
Keywords:COX-2, FUTs, Gastric cancer, H. pylori, Lewis Y, MAPKs, NSAIDs.
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.
