Recent advances in the tumour biology of the GPI-anchored carcinoembryonic antigen family members CEACAM5 and CEACAM6

On its discovery in 1965 by Gold and Freedman 1 in the blood of patients with colorectal cancer, human carcinoembryonic antigen [CEA (since re-designated CEACAM5)] was initially thought to be a tumourspecific antigen. Although CEACAM5 was subsequently found in normal tissues, its consistent overexpression in many cancers has made it a tumour marker widely used for patient management and a popular molecular target for novel cancer therapies. After the cloning of CEACAM5 cDNA in 1986 2, other CEACAM5-related cell adhesion molecules were also identified in humans and other mammalian species 3–5. The CEACAM family members are highly glycosylated proteins that belong to the immunoglobulin gene superfamily 6. In humans, the CEACAM family consists of membrane-linked and secretory glycoproteins. The former are anchored to the cell surface either by a glycophosphatidyl–inositol (GPI) anchor or a transmembrane domain. The GPIanchored members include CEACAM5 (the original CEA), CEACAM6, CEACAM7, and CEACAM8 3. Thus far, the GPI-anchored CEACAMs have been detected only in primates, and not in lower mammals 3–5,7. The enormous volume of literature describing the aberrant expression of CEACAM5 and CEACAM6 in various types of cancers, the prognostic values of such expression, and CEACAM5-targeted therapies has tended to dilute studies revealing the significant biologic functions of these antigens and their potential clinical implications. This editorial overview highlights current knowledge of the biologic functions of CEACAM5 and CEACAM6 in relation to tumorigenesis.