The biology of the 17-1A antigen (Ep-CAM)

Department of Pathology, Leiden University Medical Center, The Netherlands.
Journal of Molecular Medicine (Impact Factor: 4.74). 11/1999; 77(10):699-712. DOI: 10.1007/s001099900038
Source: PubMed

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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    • "EpCAM regulates both normal and cancer-associated events including cell-cell adhesion, cell proliferation, maintenance and regulation of non-differentiated states, migration and invasion (Figure 5) [121] [122]. In cancer cells, EpCAM is homogeneously distributed on their surface and its overexpression has been associated with cancer progression [120] [123] [124] [125]. In fact, EpCAM overexpression was appointed as an indicator of increased stage and grade, and poor prognosis in bladder cancer [125] [126]. "
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    ABSTRACT: Bladder cancer is the most common malignancy of the urinary tract, presents the highest recurrence rate among solid tumors and is the second leading cause of death in genitourinary cancers. Despite recent advances in understanding of pathophysiology of the disease, the management of bladder cancer patients remains a clinically challenging problem. Particularly, bladder tumors invading the muscularis propria and disseminated disease are often not responsive to currently available therapeutic approaches, which include surgery and conventional chemotherapy. Antibody-based therapeutic strategies have become an established treatment option for over a decade in several types of cancer. However, bladder cancer has remained mostly an "orphan disease" regarding the introduction of these novel therapeutics, which has been translated in few improvements in patients overall survival. In order to shift this paradigm, several clinical studies involving antibody-based therapeutic strategies targeting the most prominent bladder cancer-related biomolecular pathways and immunological mediators are ongoing. This systematic review explores antibody-based therapeutics for bladder cancer undergoing clinical trial and discusses the future perspectives in this field, envisaging the development of more effective guided therapeutics. Copyright © 2015. Published by Elsevier B.V.
    Journal of Controlled Release 09/2015; 214:40–61. DOI:10.1016/j.jconrel.2015.07.002 · 7.26 Impact Factor
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    • "The most highly conserved regions are the thyroglobulin repeat domain and the transmembrane region. Unlike, Trop2, which is intronless, Epcam consists of nine coding exons; Exons 1–6 encode the extracellular domain, exon 7 the transmembrane region, and exons 8–9 the intracellular tail (Balzar et al., 1999). The cysteine positions and distributions of hydrophilic and hydrophobic residues in the thyroglobulin repeat domain are conserved between TROP2 and EpCAM. "
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    • "EpCAM is a human gallbladder epithelial cell marker EpCAM is a cell surface marker that was first described in colorectal cancer (Koprowski et al., 1979). Its expression has since been found on a wide variety of epithelial cells such as keratinocytes, thymic epithelial cells and IHBD cells (Balzar et al., 1999; de Boer et al., 1999). Previously, we have determined that mouse gallbladder epithelial cells were EpCAM +, and subsequently used EpCAM to label these cells by flow cytometry (Manohar et al., 2011). "
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    ABSTRACT: There are currently no reports of identification of stem cells in human gallbladder. The differences between human gallbladder and intrahepatic bile duct (IHBD) cells have also not been explored. The goals of this study were to evaluate if human fetal gallbladder contains a candidate stem cell population and if fetal gallbladder cells are distinct from fetal IHBD cells. We found that EpCAM+CD44+CD13+ cells represent the cell population most enriched for clonal self-renewal from primary gallbladder. Primary EpCAM+CD44+CD13+ cells gave rise to EpCAM+CD44+CD13+ and EpCAM+CD44+CD13- cells in vitro, and gallbladder cells expanded in vitro exhibited short-term engraftment in vivo. Last, we found that CD13, CD227, CD66, CD26 and CD49b were differentially expressed between gallbladder and IHBD cells cultured in vitro indicating clear phenotypic differences between the two cell populations. Microarray analyses of expanded cultures confirmed that both cell types have unique transcriptional profiles with predicted functional differences in lipid, carbohydrate, nucleic acid and drug metabolism. In conclusion, we have isolated a distinct clonogenic population of epithelial cells from primary human fetal gallbladder with stem cell characteristics and found it to be unique compared to IHBD cells. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
    Stem Cell Research 02/2015; 18(3). DOI:10.1016/j.scr.2014.12.003 · 3.91 Impact Factor
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