Ep-CAM: a human epithelial antigen is a homophilic cell-cell adhesion molecule.

Abstract

Abstract. The epithelial glycoprotein 40 (EGP40, also known as GA733-2, ESA, KSA, and the 17-1A antigen), encoded by the GA-733-2 gene, is expressed on the baso-lateral cell surface in most human simple epithelia. The protein is also expressed in the vast majority of carcinomas and has attracted attention as a tumor marker. The function of the protein is unknown. We demonstrate here that EGP40 is an epithelium-specific intercellular adhesion molecule. The molecule mediates, in a Ca2+-independent manner, a homophilic cell-cell adhesion of murine cells transfected with the complete EGP40 eDNA. Two murine cell lines were tested for the effects of EGP40 expression: fibroblastic L cells and dediff-erentiated mammary carcinoma L153S cells. The expression of the EGP40 protein causes morphological changes in cultures of transfected cells-increasing intercellular adhesion of the transfectants-and has a clear effect on cell aggregating behavior in suspension aggregation assays. EGP40 directs sorting in mixed cell populations, in particular, causes segregation of the transfectants from the corresponding parental cells. EGP40 expression suppresses invasive colony growth of L cells in EHS-matrigel providing tight adhesions between cells in growing colonies. EGP40 can thus be considered a new member of the intercellular adhesion molecules. In its biological behavior EGP40 resembles to some extent the molecules of the immtmoglobulin superfamily of cell adhesion molecules (CAMs), although no immunoglobulin-like repeats are present in the EGP40 molecule. Certain structural similarities in general organization of the molecule exist between EGP40 and the lin-121Notch proteins. A possible role of this adhesion molecule in formation of architecture of epithelial tissues is discussed. To reflect the function of the molecule the name Ep-CAM for EGP40 seems appropriate.

Metastasis-association of the rat ortholog of the human epithelial glycoprotein antigen EGP314

“…Transfection with D5.7A cDNA increased the adhesive capacity of cells, even if the binding partner did not express D5.7A, which points towards heterophilic binding. The heterophilic nature of the D5.7A binding is in discordance with reports by other groups on homophilic binding of human Ep-CAM (=EGP314, GA733-2) Litvinov et al, 1994). Litvinov et al (1994) describe homophilic, Ca 2+ -independent adhesion of murine cell lines transfected with the human EGP40 cDNA, the adhesive interaction being of the strength to allow sorting of EGP-transfected from parental nontransfected lines.…”

“…The heterophilic nature of the D5.7A binding is in discordance with reports by other groups on homophilic binding of human Ep-CAM (=EGP314, GA733-2) Litvinov et al, 1994). Litvinov et al (1994) describe homophilic, Ca 2+ -independent adhesion of murine cell lines transfected with the human EGP40 cDNA, the adhesive interaction being of the strength to allow sorting of EGP-transfected from parental nontransfected lines. Instead, Fornaro et al (1995) found no evidence for homophilic binding of Trop-2 + (GA733-1) or Trop-1 + (GA733-2) cells.…”

“…Yet, D5.7A was neither expressed on thymocytes, nor on activated lymphocytes of the rat. The apparent discrepancy considering homophilic versus heterophilic binding of D5.7A/EGP314 tempted us to explore D5.7A mediated cell adhesion in a modi®ed version of the aggregation assay described by Litvinov et al (1994) as well as in dependence on the conformation of the molecule. The results of the aggregation assay, i.e.…”

“…Litvinov et al (1994) described that EGP mediates homophilic cell-cell adhesion, which has been demonstrated by cell sorting and aggregation. In a modi®ed version of the aggregation assay (Table 2), we noted the BSp73ASML cells when incubated in Ca 2+ free medium on a rotating platform had formed doublets or small aggregates of 2 ± 5 cells after 30 min of incubation at 378C.…”

Ep-CAM RNA expression predicts metastasis-free survival in three cohorts of untreated node-negative breast cancer

“…The Epithelial cell adhesion molecule (Ep-CAM) is a transmembrane glycoprotein expressed on most human epithelial cells, functioning as a homophilic cell-cell adhesion molecule [1]. Ep-CAM is a potential target for antibody based therapies [2][3][4][5].…”