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Sialyl Lewis a: a tumor-associated carbohydrate antigen involved in adhesion and metastatic potential of cancer cells.

100%

Ugorski M., Laskowska A.

2002

vol. 49

issue 2

303-311

Neoplastic transformation is often associated with characteristic changes in the expression of the sialyl Lewisa and sialyl Lewisx antigens, representing typical tumor-associated carbohydrate antigens. High amounts of sialyl Lewisa are present in human adenocarcinomas of the colon, pancreas and stomach. A growing amount of data suggests that this carbohydrate structure is the ligand for E-selectin. Sialylated Lewis structures present on the surface of tumor cells are carried by the carbohydrate chains of glycoproteins and glycolipids. There are several lines of evidence showing that sialyl Lewisa is responsible for the adhesion of human cancer cells to endothelium. E-selectin present on endothelial cells mediates these interactions. Selectins and their carbohydrate ligands can thus play an important role in the selective homing of tumor cells during metastasis. However, the presence of sialyl Lewisa antigen on the surface of tumor cells and their adhesion to E-selectin-expressing cells in in vitro adhesion assay by itself can not be directly related to metastatic properties of all cancer cells.

CEA-negative glioblastoma and melanoma cells are sensitive to cytosine deaminase/5-fluorocytosine therapy directed by the carcinoembryonic antigen promoter.

71%

Dąbrowska A., Szary J., Kowalczuk M., Szala S., Ugorski M.

vol. 51

issue 3

723-732

Recent studies have suggested that carcinoembryonic antigen (CEA)-promoter sequences are active only in CEA-positive cells, filing in the criteria for tumor specific targeting of suicide genes. However, the present study on gene therapy of colon cancer and cell-specificity of CEA promoter, provide evidence that CEA-positive and CEA-negative cells transfected with E. coli cytosine deaminase (CD) gene under the control of CEA promotor sequence are sensitive to enzyme/pro-drug therapy with 5-fluorocytosine (5-FC). Individual clones derived from the CEA-negative cell lines: melanoma Hs294T and glioblastoma T98G after transfection with CD differed profoundly in their sensitivity to 5-FC. The IC50 values for several clones of the CEA-negative cells were almost the same as for CEA-positive colon cancer cells. Such 5-FC-sensitive clones derived from the population of CEA-negative cells, present even in small number, because of the very effective bystender effect of this enzyme/pro-drug system can cause severe problems during therapy by efficiently killing surrounding normal cells. Safety is the major issue in gene therapy. Our data suggest that the safety of gene-directed enzyme pro-drug therapy (GDEPT) with CEA promoter driven expression of therapeutic genes is not so obvious as it has originally been claimed.

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2 Acta Biochimica Polonica

1 2004

1 2002

2 Ugorski M.

1 Dąbrowska A.

1 Kowalczuk M.

1 Laskowska A.

1 Szala S.

1 Szary J.

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Sialyl Lewis a: a tumor-associated carbohydrate antigen involved in adhesion and metastatic potential of cancer cells.

CEA-negative glioblastoma and melanoma cells are sensitive to cytosine deaminase/5-fluorocytosine therapy directed by the carcinoembryonic antigen promoter.