The biology of the 17-1A antigen (Ep-CAM).
ABSTRACT The glycoprotein recognized by the monoclonal antibody (mAb) 17-1A is present on most carcinomas, which makes it an attractive target for immunotherapy. Indeed, adjuvant treatment with mAb 17-1A did successfully reduce the 5 years mortality among colorectal cancer patients with minimal residual disease. Currently the antibody is approved for clinical use in Germany, and is on its way to approval in a number of other countries. New immunotherapeutic strategies targeting the 17-1A antigen are in development or even in early-phase clinical trials. Therefore, a better understanding of the biology of the 17-1A antigen may result in improved strategies for the treatment and diagnosis of human carcinomas. In this review the properties of the 17-1A antigen are discussed concerning tumor biology and the function of the molecule. This 40-kDa glycoprotein functions as an Epithelial Cell Adhesion Molecule, therefore the name Ep-CAM was suggested. Ep-CAM mediates Ca2+-independent homotypic cell-cell adhesions. Formation of Ep-CAM-mediated adhesions has a negative regulatory effect on adhesions mediated by classic cadherins, which may have strong effects on the differentiation and growth of epithelial cells. Indeed, in vivo expression of Ep-CAM is related to increased epithelial proliferation and negatively correlates with cell differentiation. A regulatory function of Ep-CAM in the morphogenesis of epithelial tissue has been demonstrated for a number of tissues, in particular pancreas and mammary gland. The function of Ep-CAM should be taken into consideration when developing new therapeutic approaches targeting this molecule.
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ABSTRACT: Dissemination of circulating tumor cells (CTCs) in blood and their hetero-adhesion to vascular endothelial bed of distant metastatic secondary organs are the critical steps to initiate cancer metastasis. The rarity of CTCs made their in vivo capture technically challenging. Current techniques by virtue of nanostructured scaffolds monovalently conjugated with a single antibody and/or drug seem less efficient and specific in capturing CTCs. Here, we report a novel platform developed to re-engineer nanoscale dendrimers for capturing CTCs in blood and interfering their adhesion to vascular endothelial bed to form micrometastatic foci. The nanoscale dendrimers were spatiotemporally accommodated with dual antibodies to target two surface biomarkers of colorectal CTCs. Physiochemical characterization, including spectra, fluorescence, electron microscope, dynamic light scattering, electrophoresis, and chromatography analyses, was conducted to demonstrate the successful conjugation of dual antibodies to dendrimer surface. The dual antibody conjugates were able to specifically recognize and bind CTCs, moderately down-regulate the activity of the captured CTCs by arresting them in S phase. The related adhesion assay displayed that the dual antibody conjugates interfered the hetero-adhesion of CTCs to fibronectin (Fn)-coated substrates and human umbilical vein endothelial cells (HUVECs). The dual antibody conjugates also showed the enhanced specificity and efficiency in vitro and in vivo in restraining CTCs in comparison with their single antibody counterparts. The present study showed a novel means to effectively prevent cancer metastatic initiation by binding, restraining CTCs and inhibiting their hetero-adhesion to blood vessels, not by traditional cytotoxic-killing of cancer cells.Theranostics 01/2014; 4(12):1250-63. · 7.81 Impact Factor
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ABSTRACT: CTCs offer and intriguing option for cancer diagnosis. By assaying for their presence in blood, rather than through biopsy or imaging technology such as mammography, cancer screening can be made cheaper, more efficient, more comprehensive, and more effective. However, an adequate method to elucidate the presence of CTCs in whole blood has yet to be determined. We purpose a microfluidic separation device based on three proteins (anti-EpCAM, anti-CAV-1, and E-selectin) to increase capture efficiency, purity, and versatility. A passive, grooved PDMS mixer is also incorporated into the design to increase frequency of contact between the cells in suspension and the protein-functionalized surface of the bed of the channel. Current microfluidic capture devices rely solely on anti-EpCAM to bind to CTCs in flow. By incorporating E-selectin, anti-CAV-1, and a passive mixer into our chip, we are able to increase capture efficiency, purity, and versatility to yield a more robust detection assay. Introduction In 2008, over half of cancer-related deaths were caused by prostate, lung, breast or colon cancer. 1 The four diseases all share the threat of metastasis – the ability to spread from the original tumor site throughout the body via circulating tumor cells (CTCs). These cells detach from the tumor site and are transported throughout the body by either the circulatory system or bone marrow. In blood, these cells are extremely hard to find (between one in ten million and one in a billion) 2 since they are mixed in with red blood cells, leukocytes, platelets, etc. Yet, they offer an extremely attractive method for cancer screening and diagnosis since they are often detectable before the symptoms of the tumor itself become apparent. As an added benefit, such a screening method would only require a small blood sample as opposed to a traditional biopsy which necessitates invasive surgery and the removal of a tissue mass. Moreover, such a method could test for the presence of metastatic cancers throughout the whole body, rather than just a particular site as current medical imaging methods (like mammography) do.
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ABSTRACT: Aim of the study was to assess the diagnostic and prognostic impact of serum EpCAM levels in patients with pancreatic adenocarcinoma (PDAC).Anticancer research 09/2014; 34(9):4741-6. · 1.71 Impact Factor