title: Cell-surface levels of human carcinoembryonic antigen are inversely correlated with colonocyte differentiation in colon carcinogenesis.
abstract: Human carcinoembryonic antigen (CEA) is overexpressed in a wide variety of epithelial malignancies including colon cancer. CEA can function in vitro as a homotypic intercellular adhesion molecule and can block the terminal differentiation of rodent myoblasts, thus raising the possibility that deregulated expression of CEA might directly contribute to malignant progression. To address this question, the expression pattern and cell-surface levels of CEA were studied during malignant transformation of the colonic epithelium in sporadic and familial adenomatous polyposis-related neoplasms. The level of immunohistochemically detected CEA was higher in 30% to 62% of microadenomas and small adenomas from familial adenomatous polyposis patients compared with adjacent normal mucosa, and this proportion was positively correlated with lesion size and degree of dysplasia. Cytofluorometric analysis of highly purified single epithelial cell suspensions from freshly excised carcinomas versus adjacent normal tissue demonstrated up to a 20-fold increase of mean cell-surface CEA in a group of colon carcinomas representative of the overall majority of such tumors--from Dukes' stages A to D and ranging mainly from well to moderately differentiated, the degree of overproduction was inversely correlated with tumor differentiation and directly correlated with stage. A marked tendency toward nonpolarized versus apical cell-surface expression with progression was also noted. Nonspecific cross-reacting antigen (NCA), a CEA family member, is also a homotypic adhesion molecule and blocks terminal myogenic differentiation, whereas biliary glycoprotein is a CEA family adhesion molecule that does not. Cell-surface NCA showed even greater overexpression (up to 70-told) in dedifferentiated tumors, whereas total-cell biliary glycoprotein showed approximately 2-fold lower levels than was normal in more differentiated tumors and approximately 2-fold higher levels than in further progressed tumors. These results therefore support the suggestion that CEA and NCA can directly contribute to colon carcinogenesis by inhibiting colonocyte differentiation.
authors.affiliation: Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Ilantzis
authors.forename: S
authors.initials: S
authors.lastname: Jothy
authors.forename: L C
authors.initials: LC
authors.lastname: Alpert
authors.forename: P
authors.initials: P
authors.lastname: Draber
authors.forename: C P
authors.initials: CP
authors.lastname: Stanners
mesh_terms: D000236:Adenoma / Q000737:chemistry / Q000473:pathology; D015703:Antigens, CD; D000951:Antigens, Neoplasm / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002272:Carcinoembryonic Antigen / Q000032:analysis / Q000096:biosynthesis*; D002277:Carcinoma / Q000737:chemistry* / Q000473:pathology; D015815:Cell Adhesion Molecules; D002454:Cell Differentiation; D003108:Colonic Diseases / Q000473:pathology; D003110:Colonic Neoplasms / Q000737:chemistry* / Q000473:pathology; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D019084:Fluorescent Antibody Technique, Indirect; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000096:biosynthesis; D009367:Neoplasm Staging; D011230:Precancerous Conditions / Q000737:chemistry / Q000473:pathology
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C069847:CD66 antigens; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D008562:Membrane Glycoproteins