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.

Prevalence and Correlation with Clinical Diseases ofHelicobacter pylori cagAandvacAGenotype among Gastric Patients from Northeast China

“…Genetic diversity may play an important role in genotypic variation of H. pylori , which makes it more virulent with diverse pathogenicity [3]. H. pylori carries different virulence factors, such as urease, flagellar, vacuolating cytotoxin A (VacA), and cytotoxin-associated gene A (CagA), that play an important role in invasion, colonization, and cell proliferation [4, 5]. High genetic variations of cagA and vacA gene are associated with more severe infectionsof H. pylori [6].…”

Moving a Carbohydrate Mimetic Peptide into the clinic

“…Antibodies directed against LeY side chains of ErbB receptors are capable of inhibiting ErbB-mediated signaling, 6 while other anti-LeY mAbs mediate the MAPK signaling pathway. 8 Likewise some gangliosides, such as GD2, can facilitate cell attachment. 9 Anti-GD2 mAb are noted to affect α2β1 integrin-mediated platelet adhesion to collagen and phosphotyrosine signaling of FAK.…”

Targeting tumor-associated carbohydrate antigens: a phase I study of a carbohydrate mimetic-peptide vaccine in stage IV breast cancer subjects

“…We have shown previously that immunization with a plant lectin-reactive mimotope led to generation of apoptotic antibodies in a mouse model [ 8 ]. Anti-LeY and -GD2 antibodies are expected to negatively affect tumor-cell viability through induction of apoptosis and inhibition of growth [ 19 , 23 , 32 , 33 ]. Therefore we examined whether serum antibodies from immunized subjects affect viability of human breast cancer cell lines in vitro .…”