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.
"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. "
"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). "
"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. "
[Show abstract][Hide abstract] ABSTRACT: Background:
Trop2 was first discovered as a biomarker of invasive trophoblast cells. Since then most research has focused on its role in tumourigenesis because it is highly expressed in the vast majority of human tumours and animal models of cancer. It is also highly expressed in stem cells and in many organs during development.
We review the multifaceted role of Trop2 during development and tumourigenesis, including its role in regulating cell proliferation and migration, self-renewal, and maintenance of basement membrane integrity. We discuss the evolution of Trop2 and its related protein Epcam (Trop1), including their distinct roles. Mutation of Trop2 leads to gelatinous drop-like corneal dystrophy, whereas over-expression of Trop2 in human tumours promotes tumour aggressiveness and increases mortality. Although Trop2 expression is sufficient to promote tumour growth, the surprising discovery that Trop2-null mice have an increased risk of tumour development has highlighted the complexity of Trop2 signaling. Recently, studies have begun to identify the mechanisms underlying TROP2’s functions, including regulated intramembrane proteolysis or specific interactions with integrin b1 and claudin proteins.
Understanding the mechanisms underlying TROP2 signaling will clarify its role during development, aid in the development of better cancer treatments and unlock a promising new direction in regenerative medicine.
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