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

J Mol Med (Berl). 1999 Oct;77(10):699-712. doi: 10.1007/s001099900038.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • Antigens, Neoplasm / analysis
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / physiology*
  • Biomarkers, Tumor / analysis
  • Breast / chemistry
  • Breast / embryology
  • Cadherins / physiology
  • Carcinoma / chemistry
  • Carcinoma / diagnosis
  • Carcinoma / immunology*
  • Carcinoma / therapy
  • Cell Adhesion / physiology
  • Cell Adhesion Molecules / analysis
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / immunology
  • Cell Adhesion Molecules / physiology*
  • Cell Differentiation
  • Cell Transformation, Neoplastic
  • Chromosomes, Human, Pair 4 / genetics
  • Epithelial Cell Adhesion Molecule
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Evolution, Molecular
  • Female
  • Fetal Proteins / physiology
  • Gene Expression Regulation, Neoplastic
  • Genes
  • Humans
  • Immunohistochemistry
  • Immunotherapy
  • Male
  • Mice
  • Mice, Transgenic
  • Morphogenesis
  • Multigene Family
  • Organ Specificity
  • Pancreas / chemistry
  • Pancreas / embryology
  • Protein Conformation
  • Protein Structure, Tertiary

Substances

  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Cadherins
  • Cell Adhesion Molecules
  • Epithelial Cell Adhesion Molecule
  • Fetal Proteins