EpCAM (NCBI Reference Sequence NM_002354.2; also called GA733, KSA, 17-1A antigen, or CD326) is a 40 kDa epithelial cell surface glycoprotein that mediates Ca2+ independent homophilic cell-cell adhesion. The epithelium of healthy individuals expresses EpCAM, with the exception of squamous epithelium and of specific epithelial cells of adult hepatocytes and keratinocytes. EpCAM is over-expressed to varying degrees in numerous human carcinomas, cancer-initiating cells, and in progenitor and normal stem cells. It has recently been shown that EpCAM upregulates c-myc, cyclin A and E and it influences the cell cycle and enhances cell proliferation. In addition, it is involved in the nuclear Wnt-signaling pathway that also promotes cell proliferation and tumorigenesis. Though the exact role of EpCAM is elusive in ovarian cancer progression, the EpCAM over expression significantly correlates with decreased survival rate in patients at stage III/IV of the disease and over expression of EpCAM in breast and gallbladder cancer has a strong correlation with poor prognosis. Anti-EpCAM antibodies were used to identify circulating tumor cells in the blood of cancer patients, and to provide prognostic information that allows treatment of patients. In addition, the direct association of EpCAM with the progression of ovarian cancer suggested that it may serve as potential therapeutic target for the treatment of ovarian cancer and different approaches have been established to target EpCAM. EpCAM antibodies such as MT201 efficiently eliminate cancer cells from ovarian cancer patients. For example, Catumaxomab has been approved for the treatment of malignant ascites and it has been used for epithelial ovarian and non-ovarian cancers. Although, anti-EpCAM monoclonal antibodies provide protection against cancer, the antibody dependent cytotoxicity relies on the CH2 domain of the antibody that varies significantly from batch to batch during antibody production. In addition, anti-EpCAM antibodies failed to provide any clinical protection against colorectal and prostate cancer due to the large size of the antibody which confines distribution and delivery. Hence, better and more general strategies for the targeted repression of EpCAM are required.
Nunna S, Reinhardt R, Ragozin S, Jeltsch A. Targeted Methylation of the Epithelial Cell Adhesion Molecule (EpCAM) Promoter to Silence Its Expression in Ovarian Cancer Cells. Tost J, ed. PLoS ONE. 2014;9(1):e87703.