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-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.
Highlights
The use of mAbs as adjuvant in cancer chemotherapy has drawn considerable interest because of the success of several novel agents with a broad range of targets
To determine whether the immunoreaction of anti-epithelial cell adhesion molecule (EpCAM) mAb with RAW264.7 cells is inhibited to cancer cell growth, the inhibitory effect of anti-EpCAM mAb on SW620 cancer cell growth was analyzed by direct counting
To determine whether the inhibition of SW620 cell growth by anti-EpCAM mAb was due to the induction of apoptotic cell death, we evaluated the changes in apoptosis by double staining with DAPI and TdT-mediated dUTP nick and labeling (TUNEL); we examined the TUNEL-labeled cells under a fluorescence microscope
Summary
The use of mAbs as adjuvant in cancer chemotherapy has drawn considerable interest because of the success of several novel agents with a broad range of targets. Several immunological agents have been discovered, a comprehensive understanding of the mechanism of action, the optimal dose, or administration timing is absent (Dyer, 1999; Sievers et al, 2001; Dillman, 2002). Models based on tumor destruction by antigendependent cell-mediated cytotoxity or by complementdependent cytotoxicity and idiotypic networks have been developed to explain the effectiveness of mAbs. A mAb directed against epithelial cell adhesion molecule (EpCAM) is currently under development. The human colorectal carcinoma (CRC)-associated antigen GA733, named CO17-1A/EpCAM/ KSA/KS1-4, is highly expressed in human CRCs and is a useful passive immunotherapy target in CRC patients
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