ENZYMATIC BASIS FOR SIALYL-TN EXPRESSION IN HUMAN COLON-CANCER CELLS

Sialyl-Tn antigen (SA alpha 2-6 GalNAc alpha-Ser/Thr) is expressed as a cancer-associated antigen on the surface of cancer cells and its exp ression correlates with a poor prognosis in patients with colorectal a nd other adenocarcinomas, To understand the enzymatic basis of sialyl- Tn (STn) antigen expression, we used two clonal cell lines, LSB and LS C, derived from LS174T human colonic cancer cells. LSC cells express o nly the truncated carbohydrate antigen Tn (GalNAca-Ser/Thr) and sialyl -Tn on their mucin molecules, whereas LSB cells express elongated olig osaccharide chains, Both cell lines demonstrated similar activities of glycosyltransferases involved in the biosynthesis of elongated and te rminal structures of complex O-glycans, However, LSC cells were unable to synthesize core 1 (Gal beta 1-3GalNAc-) because the ubiquitous enz yme activity of UDP-Gal:GalNAc-R beta 3-Gal-transferase (core 1 beta 3 -Gal-transferase) was lacking, Core 1 beta 3-Gal-transferase could not be reactivated in LSC cells by treatment with sodium butyrate or by i n vivo growth of LSC cells in nude mice, In contrast, LSB cells were a ble to synthesize and process core 1 and core 2 (GlcNAc beta 1-6 (Gal beta 1-3) GalNAc-), LSC cells represent the first example of a non-hem atopoietic cell line which lacks core 1 PS-Gal-transferase activity. T he lack of core 1 beta 3-Gal-transferase in LSC cells explains why the y are incapable of forming the common mucin O-glycan core structures a nd are committed to synthesizing the short Tn and STn oligosaccharides , These findings suggest that the activity of core 1 beta 3-Gal-transf erase is an important determinant of the STn phenotype of colon cancer cells.