GLYCOBIOLOGY OF SULFATED GLYCOCONJUGATES IN CANCER

最近，癌症相关的糖脂和糖蛋白含有

Recently, cancer-associated glycolipids and glycoproteins containing sulfate residue (or residues) have attracted much attention. The presence of these sulfated glycoconjugates raises some very important and interesting questions: Is aberrant sulfation a characteristic of certain malignancies; What type of sulfotransferases are involved in the expression of these sulfoglycoconjugates? This proposal centers at the glycobiology of sulfosaccharides in order to seek answers to these questions. Our prime interest is in the biochemical aspects, and in the synthesis of carbohydrate structures required for these studies. We propose to study different sulfotransferases such as; (a) Galactose 3-O- sulfotransferase, which acts upon Ga1beta1yields3Ga1NAcalpha yields linked compounds. We have already demonstrated the existence of this enzyme activity in human ovarian tissues and human spleen. (b) Sulfotransferase capable of acting on Ga1beta1 yields 4G1cNAc and Ga1beta1yields3G1cNAc to give SE-3Ga1beta1yields4G1cNAc and SE-3Ga1beta1yields6G1cNAc, respectively. Human colon tissues contain this enzyme. (c) 6-O-Sulfotransferase involved in the assembly of the 6'-sulfated Lewis (x) moiety [NeuAcalpha2 yields 3 (SE-6Ga1)beta1 yields4(Eucalpha1 yields 3) G1cNAc]. (d) Sulfotransferase which acts on G1cNAcbeta1 yields 3 Ga1beta1yields OMe to give SE-6G1cNAcbeta1yields3Ga1beta1yieldsOMe. We are interested in utilizing different tumor cell lines and both normal and cancerous human tissues a source material for screening and demonstrating the existence of sulfotransferase. Among these sources, those displaying appreciable activity will become candidates for further study. Our synthetic saccharides having sulfate situated at different positions (isomeric sulfated saccharides) will be particularly useful as reference compounds for the characterization and analysis of sulfotransferase product. The identification of sulfotransferase activities will shed new light on the biosynthetic pathways of glycoconjugates, especially those glycoconjugates containing sulfate, fucose and sialic acid. These studies will provide information toward the synthesis of target ligands for cell- adhesion (selectin) molecules. A successful outcome of the proposed program will open various avenues for other important investigations.