[Carbohydrate antigens in carcinoma invasion and metastasis]

Human colorectal carcinomas with increased metastatic potential and with poor prognosis are characterized by high content of sialyl-Lewis X carbohydrate antigen as detected by monoclonal antibody (mAb) FH6. The levels of these carbohydrate antigens apparently increase during colorectal carcinoma progression from nonmetastatic to metastatic tumors and inversely correlate with post operative survival of colon carcinoma patients. Cell lines have been selected for high and low levels of cell surface sialyl-Lewis X antigen using mAb FH6. The high expresser cells adhere strongly to cytokine-activated endothelial cells apparently through E-selectin. The high expresser cells are also adhesive to sections of human livers, although involvement of selectins in this process is unknown. Increased expression of sialyl-Lewis X antigens on the surface of these high expresser variant cells is apparently due to increased alpha 1,3-fucosyltransferase, a biosynthetic enzyme presumable responsible for the final step of the production of sialyl-Lewis X antigens. Human fucosyltransferase VI cDNA has been stably transfected into the low expresser variant cells. alpha 1,3-Fucosyltransferase activity, cell surface sialyl-Lewis X carbohydrate antigen, and adhesion to activated endothelial cells have been showed to increase in these transfectant cells. Furthermore, these cells show dramatic increase in their liver metastatic potential when it is tested by the intrasplenic injection into nude mice. We propose that carbohydrate antigens with unique peripheral epitopes serve as unique molecular phenotypes that determine colorectal cancer metastasis.