REDUCTION OF METASTATIC PROPERTIES OF BL6 MELANOMA-CELLS EXPRESSING TERMINAL FUCOSE-ALPHA-1-2-GALACTOSE AFTER ALPHA-1,2-FUCOSYL-TRANSFERASECDNA TRANSFECTION

We reported previously that transfection of BL6 melanoma cells that do not express the alpha 1,3-galactosyltransferase (alpha 1,3GT) gene wi th the alpha 1,3GT cDNA resulted in synthesis and expression of ar-gal actosyl epitopes (Gal alpha 1-3Gal beta 1-4GlcNAc-R) and an impairment of their metastatic potentials, It was of interest to test whether in hibition of metastatic properties of BL6 melanoma cells is specificall y associated with the appearance of the terminal alpha-Gal or whether capping N-acetyllactosamine with another oligosaccharide would also af fect the metastatic properties of BL6 melanoma cells, For this purpose , BL6-2 clone isolated from B16BL6 melanoma was transfected with the a lpha 1,2-fucosyltransferase (alpha 1,2FT) cDNA, The alpha 1,2FT cataly zes a transglycosylation reaction, resulting in syntheses of the Fuc a lpha 1-2Gal beta 1-4GlcNAc-R structure, which is known as the ii antig en of O blood group in humans and is also synthesized in some cells of mice, Transfection of BL6 melanoma cells with the alpha 1,2FT cDNA re sulted in the appearance of the terminal Fuc alpha 1-2Gal beta 1-4GlcN Ac-R epitopes reacting with the Ulex europneus agglutinin lectin, In p arallel, the transfected cells shelved a decrease in N-acetyllactosami ne sialylation, Decline in sialylation of the transfected cells is lik ely to be the result of competition between alpha 1,ZFT and alpha 2,3- or alpha 2,6-sialyltransferases for the common substrate N-acetyllact osamine (Gal beta 1-4GlcNAc-R) on N-linked carbohydrate chains of glyc oproteins and glycolipids. The alpha 1,2FT-transfected BL6-2 cells sho wed an increase In homotypic aggregation, In parallel, metastatic abil ity of the alpha 1,2FT-transfected BL6-2 cells was reduced significant ly in the immunocompetent as well as immunosuppressed (X-irradiated) m ice, Thus, these data imply that capping N-acetyllactosamine with alph a Gal or alpha Fuc and the corresponding reduction in sialylation of B L6-2 melanoma cells were associated with reduction of their metastatic potential.