title: Carcinoembryonic antigen is expressed on endothelial cells. A putative mediator of tumor cell extravasation and metastasis.
abstract: Carcinoembryonic antigen (CEA) is a highly glycosylated cell surface protein. It is produced in large amounts in essentially all colon and several other adenocarcinomas. It has therefore been widely used as a clinical tumor marker. CEA is also a member of the immunoglobulin superfamily. Members of this family, such as ICAM-1, ICAM-2, VCAM-1 and NCAM, are known to participate in cell-cell adhesion. Similarly, the intercellular adhesion properties of CEA have been documented: it has been shown to mediate homotypic adhesion of cultured human colon adenocarcinoma cell lines. In this study we show for the first time that CEA is expressed on cultured human umbilical vein endothelial cells and on the endothelial cell line Ea.hy926. The expression of CEA on cultured endothelial cells can be enhanced by TNF-alpha or IFN-gamma, and decreased by IL-4. We demonstrate using immunohistochemistry that anti-CEA monoclonal antibody reacted with FVIII-positive endothelium in tissue sections prepared from lymph nodes. Finally, we were able to show that CEA-positive breast carcinoma cells bind to purified CEA protein, whereas CEA-negative breast carcinoma cells do not. These results reveal for the first time that endothelial cells express CEA on the cell surface and suggest that CEA-expressing adenocarcinomas could adhere to endothelial cells via CEA-CEA interaction, thus facilitating tumor cell extravasation and hematogenic metastasis.
authors.affiliation: Department of Bacteriology and Immunology, University of Helsinki, Finland.
authors.forename: M L
authors.initials: ML
authors.lastname: Majuri
authors.forename: M
authors.initials: M
authors.lastname: Hakkarainen
authors.forename: T
authors.initials: T
authors.lastname: Paavonen
authors.forename: R
authors.initials: R
authors.lastname: Renkonen
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000276:immunology; D001943:Breast Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D002272:Carcinoembryonic Antigen / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000737:chemistry* / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008198:Lymph Nodes / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma