[Ectopic expression of carbohydrate antigens that determine the metastatic potential of human colorectal carcinoma].
Highly malignant and metastatic tumor cells are thought to arise within primary tumors and become predominant during cancer progression. We demonstrated, by the analysis of > 500 surgical specimens, that colorectal carcinomas with increased metastatic potential were characterized by an increased expression of sialyl-Le(x) antigens expressed on mucins. The biological role of sialyl-Le(x) antigens expressed on mucins produced by colon carcinoma cells has been investigated using variant cell lines selected for their expression of this antigen. KM12-HX and KM12-LX, high and low expresser variant cells, differed in their metastatic potential in nude mice after intrasplenic injection. KM12-HX cells contain higher levels of polyA+mRNA for alpha(1-3/4) fucosyltransferase than KM12-LX cells. Sialyl-Le(x) antigenic carbohydrate chains were attached to mucins as well as glycoproteins with various M(r). KM12-HX cells adhered more strongly than KM12-LX cells to human umbilical vein endothelial cells treated with tumor necrosis factor-alpha and to mouse hepatic sinusoidal endothelial cells. We have retrospectively evaluated post-operative survival of colon carcinoma patients for their sialyl-Le(x) antigen levels in the primary tumors according to the percentage of stained cells by specific antibodies. The adjusted survival rate of the patients with high levels of sialyl-Le(x) antigen in their primary tumors was much lower due to recurrence and metastasis than that of the patients with tumors containing low levels of sialyl-Le(x) antigen. The results suggested that sialyl-Le(x) antigen has a potential to be used as a predictive marker for colorectal cancer metastasis.
Irimura
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Div. of Chemical Toxicology and Immunochemistry, Faculty of Pharmaceutical Sciences, University of Tokyo.
D000818:Animals; D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism / Q000502:physiology; D014408:Biomarkers, Tumor / Q000378:metabolism; D002448:Cell Adhesion; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology*; D005647:Fucosyltransferases / Q000378:metabolism; D006801:Humans; D016256:Lewis X Antigen / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D011379:Prognosis
D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; D016256:Lewis X Antigen; D005647:Fucosyltransferases