Induction of carcinoembryonic antigen and its crossreactive gene products in human colonic adenomas and carcinomas by transforming growth factor-beta.
The inducing effect of transforming growth factor-beta (TGF-B) on carcinoembryonic antigen (CEA) secretion and the cellular expression of CEA and CEA crossreactive glycoproteins (CEA-GLY) was examined from a panel of human colonic cell lines with different phenotypic classification. This panel included carcinomas with dissimilar differentiation characteristics and metastatic behavior, and premalignant adenomas derived from colonic polyps. A great degree of heterogeneity was observed in the endogenous levels of CEA secretion and the cellular expression of CEA and CEA-GLY species. The response profiles of the different cell lines to TGF-B treatment were also found to be heterogenous. However, TGF-B was able to induce CEA secretion and up-modulated the cellular expression of CEA and CEA-GLY from a majority of the cells tested. More importantly, TGF-B was able to exert these effects on carcinoma cells that secrete or express minimal or nondetectable amounts of these glycoproteins. These biologic modifying effects of TGF-B may have potential in augmenting the efficacy of CEA as a colon cancer marker, and in antibody-directed radioimaging and therapeutics. Further investigation in vivo in an experimental animal model system is warranted.
Chakrabarty
S
S
Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030.
Mustain
S
S
Willson
J K
JK
D000236:Adenoma / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D002277:Carcinoma / Q000473:pathology*; D003110:Colonic Neoplasms / Q000473:pathology*; D003111:Colonic Polyps / Q000473:pathology; D003429:Cross Reactions; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D006801:Humans; D005810:Multigene Family; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015291:Transforming Growth Factors / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D006023:Glycoproteins; D009363:Neoplasm Proteins; D015291:Transforming Growth Factors