Metastatic potential of human CX-1 colon adenocarcinoma cells is dependenton the expression of sialosyl Le(a) antigen

Several lines of evidence indicate that sialosyl Le(a), tumor-associated ca rbohydrate antigen present on human colon carcinoma cells, is involved in f ormation of metastases. To study the role of this carbohydrate structure in development of metastases, we have used the clone of human colon carcinoma CX-1 cells transfected with antisense expression vector containing fragmen t of cDNA for alpha 1,3/4-fucosyltransferase (PT III), which is involved in synthesis of sialosyl Le(a) tetrasaccharide. It has been reported previous ly that, in contrast to the parental cells, the antisense-transfected CX-1, 1AS5 cells do not express sialosyl Le(a) and do not adhere to E-selectin-ex pressing CHO cells, In the present work we have studied the formation of li ver metastases by CX-1.1AS5 cells after their orthotopic or intrasplenic im plantation into athymic nu/nu mice, After orthotopic implantation of sialos yl Lea-negative colon carcinoma CX-1.1AS5 cells, the number of mice with li ver metastases was markedly lower (21% of mice) in comparison with their nu mber after implantation of the parental CX-1.1 cells (85% of mice), However , no differences in ability to form colonies in liver were observed between parental CX-1.1 cells and antisense-transfected CX-1.1AS5 cells after intr asplenic inoculation, The liver metastases were formed in 89% and 84% of mi ce, respectively, Our data support the thesis on the importance of sialosyl Le(a) antigen expression in the development of liver metastases by colon c ancer cells, and indicate the role of transplantation route and primary tum or localization in formation of metastases.