Glycolipid glycosyltransferases in human embryonal carcinoma cells during retinoic acid induced differentiation

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Abstract
Retinoic acid induced differentiation of TERA-2-derived human embryonal carcinoma cells is accompanied by a dramatic reduction of extended globo-series glycolipids, including galactosyl globoside, sialylgalactosyl globoside, and globo-A antigen (each recognized by specific MoAbs). Associated with these glycolipid changes, the activities of two key enzymes, .alpha.1 .fwdarw. galactosyltransferase (for synthesis of globotriaosyl core structure) and .beta.1 .fwdarw. 3galactosyltransferase (for synthesis of galactosyl globoside), were found to be reduced 3- to 4-fold. The latter enzyme plays a key role in the synthesis of extended globo-series structures, and its characterization has not been reported previously. Therefore, its catalytic activity was studied in detail, including substrate specificity, detergent and phospholipid effects, pH and cation requirements, and apparent Km. During retinoic acid induced differentiation, a series of Lex glycolipid antigens (recognized by anti-SSEA-1 antibody) and their core structures (lacto-series type 2 chains) increase dramatically. In parallel with these changes in glycolipid expression, the activities of two key enzymes, .beta.1 .fwdarw. 3N-acetylglucosaminyltransferase (for extension of lacto-series type 2 chain) and .alpha.1 .fwdarw. 3-fucosyltransferase (for synthesis of Lex structure), were found to increase by 4- and 2-fold, respectively. Similarly, an increase in the expression of several gangliosides (e.g., GD3 and GT3) during retinoic acid induced differentiation was mirrored by a 4-fold increase in the activity of .alpha.2 .fwdarw. 3-sialyltransferase (for synthesis of gangli core structure, GM3). The results suggest a coordinate regulation of key glycosyltransferases involved in core structure assembly and terminal chain modification. Changes in the expression of these glycosyltransferases may mediate the changes in glycolipid antigen expression observed during embryonal carcinoma cell differentiation and may provide an important basis for changes in cell surface phenotype during embryogenesis.