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Abstract

Several lines of evidence indicate that sialosyl Le(a), tumor-associated carbohydrate antigen present on human colon carcinoma cells, is involved in formation 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 fragment of cDNA for alpha1,3/4-fucosyltransferase (FT III), which is involved in synthesis of sialosyl Le(a) tetrasaccharide. It has been reported previously 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-expressing CHO cells. In the present work we have studied the formation of liver metastases by CX-1.1AS5 cells after their orthotopic or intrasplenic implantation into athymic nu/nu mice. After orthotopic implantation of sialosyl Le(a)-negative colon carcinoma CX-1.1AS5 cells, the number of mice with liver metastases was markedly lower (21% of mice) in comparison with their number after implantation of the parental CX-1.1 cells (86% 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 intrasplenic inoculation. The liver metastases were formed in 89% and 84% of mice, respectively. Our data support the thesis on the importance of sialosyl Le(a) antigen expression in the development of liver metastases by colon cancer cells, and indicate the role of transplantation route and primary tumor localization in formation of metastases.

Gastric Cancer Cell Glycosylation as a Modulator of the ErbB2 Oncogenic Receptor

“…On the other hand, the abnormal expression of specific glycoconjugates by malignant cells benefits from a degree of unprecedented specificity and constitutes, in this way, a foreseeable promising source of novel diagnostic, prognostic and therapeutic molecular tools. The SLe a carbohydrate antigen is deeply involved in multiple molecular processes underlying neoplastic transformation [ 44 , 45 , 46 , 47 , 48 ]. Moreover, the frequent upregulation of circulating SLe a -modified glycoconjugates in individuals bearing gastrointestinal tumors led to the clinical implementation of the CA 19.9 serological assay.…”

Lectins from the Red Marine Algal SpeciesBryothamnion seaforthiiandBryothamnion triquetrumas Tools to Differentiate Human Colon Carcinoma Cells

“…The EB3 variant was subjected to further selection by inoculation in vivo, in athymic NCr nu/nu male mice, by various routes of inoculation (intravenously, intrasplenically, or orthotopically), to select differentially metastasizing variants [20]. After repeated passages, several highly metastatic cells variants were obtained.…”

Selectin Ligands Sialyl-Lewis a and Sialyl-Lewis x in Gastrointestinal Cancers

“…In colon cancer patients, increased expression of sLe x and sLe a correlated with metastasis and poor survival [140,141,142,143]. Down-regulation of sLe expression by knock-down of key glycosyltransferases in cancer cell lines resulted in reduced selectin binding and reduced metastatic ability [11,12,144], while forced expression of sLe antigens by gene transfer increased adhesion to selectins in vitro and metastatic ability in vivo [10]. The role of selectins in the metastatic process was confirmed by the finding that the formation of experimental pulmonary metastases could be inhibited by the use of peptides mimicking sLe a and was inhibited in E-selectin- knock-out mice [145].…”