Exp Mol Med.  2011 Dec;43(12):693-701. 10.3858/emm.2011.43.12.080.

Relationship between ganglioside expression and anti-cancer effects of the monoclonal antibody against epithelial cell adhesion molecule in colon cancer

• Kwak DH
• Ryu JS
• Kim CH
• Ko K
• Ma JY
• Hwang KA
• Choo YK

• KMID: 1058707
• DOI: http://doi.org/10.3858/emm.2011.43.12.080

Abstract

The human colorectal carcinoma-associated GA733 antigen epithelial cell adhesion molecule (EpCAM) was initially described as a cell surface protein selectively expressed in some myeloid cancers. Gangliosides are sialic acid-containing glycosphingolipids involved in inflammation and oncogenesis. We have demonstrated that treatment with anti-EpCAM mAb and RAW264.7 cells significant inhibited the cell growth in SW620 cancer cells, but neither anti-EpCAM mAb nor RAW264.7 cells alone induced cytotoxicity. The relationship between ganglioside expression and the anti-cancer effects of anti-EpCAM mAb and RAW264.7 was investigated by high-performance thin-layer chromatography. The results demonstrated that expression of GM1 and GD1a significantly increased in the ability of anti-EpCAM to inhibit cell growth in SW620 cells. Anti-EpCAM mAb treatment increased the expression of anti-apoptotic proteins such as Bcl-2, but the expression of pro-apoptotic proteins Bax, TNF-alpha, caspase-3, cleaved caspase-3, and cleaved caspase-8 were unaltered. We observed that anti-EpCAM mAb significantly inhibited the growth of colon tumors, as determined by a decrease in tumor volume and weight. The expression of anti-apoptotic protein was inhibited by treatment with anti-EpCAM mAb, whereas the expression of pro-apoptotic proteins was increased. These results suggest that GD1a and GM1 were closely related to anticancer effects of anti-EpCAM mAb. In light of these results, further clinical investigation should be conducted on anti-EpCAM mAb to determine its possible chemopreventive and/or therapeutic efficacy against human colon cancer.

Keyword

antibodies, monoclonal; apoptosis; colon neoplasms; EPCAM protein, human; gangliosides; macrophages

MeSH Terms

Animals
Antibodies, Monoclonal/*immunology/*therapeutic use
Antigens, Neoplasm/*immunology
Apoptosis/drug effects
Cell Adhesion Molecules/*immunology
Cell Line
Cell Line, Tumor
Cell Proliferation/drug effects
Colon/drug effects/immunology/metabolism/pathology
Colonic Neoplasms/*drug therapy/genetics/*immunology/pathology
Gangliosides/genetics/*immunology
Gene Expression Regulation, Neoplastic/drug effects
Humans
Male
Mice
Mice, Inbred BALB C