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

• Published in: Experimental & molecular medicine Vol. 43; no. 12; pp. 693 - 701
• Main Authors: Kwak, Dong Hoon, Ryu, Jae-Sung, Kim, Chang-Hyun, Ko, Kisung, Ma, Jin Yeul, Hwang, Kyung-A, Choo, Young-Kug
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 31.12.2011; Springer Nature B.V; Korean Society for Biochemistry and Molecular Biology; 생화학분자생물학회
• Subjects: Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - therapeutic use; Antigens, Neoplasm - immunology; Apoptosis - drug effects; Biomedical and Life Sciences; Biomedicine; Cell Adhesion Molecules - immunology; Cell Line; Cell Line, Tumor; Cell Proliferation - drug effects; Colon - drug effects; Colon - immunology; Colon - metabolism; Colon - pathology; Colonic Neoplasms - drug therapy; Colonic Neoplasms - genetics; Colonic Neoplasms - immunology; Colonic Neoplasms - pathology; Epithelial Cell Adhesion Molecule; Gangliosides - genetics; Gangliosides - immunology; Gene Expression Regulation, Neoplastic - drug effects; Humans; Male; Medical Biochemistry; Mice; Mice, Inbred BALB C; Molecular Medicine; Original; Stem Cells; 생화학; antibodies, monoclonal; gangliosides; apoptosis; macrophages; colon neoplasms; EPCAM protein, human
• ISSN: 1226-3613; 2092-6413
• DOI: 10.3858/emm.2011.43.12.080

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-α, 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.