The biology of the 17-1A antigen (Ep-CAM).
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.
Balzar
M
M
Department of Pathology, Leiden University Medical Center, The Netherlands.
Winter
M J
MJ
de Boer
C J
CJ
Litvinov
S V
SV
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000032:analysis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D014408:Biomarkers, Tumor / Q000032:analysis; D001940:Breast / Q000737:chemistry / Q000196:embryology; D015820:Cadherins / Q000502:physiology; D002277:Carcinoma / Q000737:chemistry / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D000071858:Epithelial Cell Adhesion Molecule; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D019143:Evolution, Molecular; D005260:Female; D005326:Fetal Proteins / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D005796:Genes; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis; D005810:Multigene Family; D009928:Organ Specificity; D010179:Pancreas / Q000737:chemistry / Q000196:embryology; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015820:Cadherins; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D005326:Fetal Proteins