Fucosyltransferase activity in metastasizing and nonmetastasizing rat mammary carcinomas.
Fucosyltransferase levels in 6 established strains of spontaneously metastasizing rat mammary tumors (STMT-058, MT-449, DMBA-4, SMT-077, TMT-081, and SMT-2A) were compared with 4 nonmetastasizing strains (MT-W9B, MT-W9A, MT-100, and MT-66) as controls. Two acceptors were prepared from fetuin for the assay, one by acid hydrolysis of N-acetylneuraminic acid and the other by the stepwise removal of N-acetylneuraminic acid and penultimate galactose by Smith degradation. The enzyme that transfers fucose to the first acceptor was designated fucosyltransferase A, whereas the one that uses the second acceptor was designated fucosyltransferase B. Both types of fucosyltransferases were found in this rat mammary tumor system. Whereas the levels of fucosyltransferase A in the 2 tumor groups were comparable, those of fucosyltransferase B were sixfold to sevenfold higher in the metastasizing tumors. This difference in the level of fucosyltransferase B was not caused either by differential hydrolysis of GDP-fucose by pyrophosphatase in the 2 groups or by hydrolysis of the product by fucosidases. Presence of any other inhibitor(s) or activator(s) of fucosyltransferase was excluded by mixing experiments. Optimal conditions for the assay of this enzyme were determined in a representative strain from each group. Under all circumstances, the activity of fucosyltransferase B was higher in the metastasizing tumors. The enzyme was inhibited by nucleoside diphosphates and triphosphates, and guanosine nucleotides were the most efficient inhibitors. Subcellular distributions of the two fucosyltransferases were similar, 35-50% of the enzyme activity being present in the crude microsomes. When plasma membrane factions were prepared from the microsomes, the major part (50-70%) of the enzyme was associated with the light and heavy plasma membrane fractions. Increased activity of fucosyltransferase B in the group of metastasizing tumors may have reflected faster synthesis and shedding of fucose-containing glycoprotein antigens. Similar molecules possibly were also synthesized in the nonmetastasizing cells but at a much slower rate, because the antigen is not easily lost from the cell surface. Any alteration of the specificity of this focosyltransferase in the metastasizing tumors, in addition, may have caused antigen modulation.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D005260:Female; D005690:Galactose / Q000378:metabolism; D006154:Guanosine Diphosphate Fucose; D006602:Hexosyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology*; D009362:Neoplasm Metastasis / Q000201:enzymology*; D009711:Nucleotides / Q000494:pharmacology; D051381:Rats; D012794:Sialic Acids / Q000378:metabolism; D013379:Substrate Specificity; D000509:alpha-Fetoproteins / Q000378:metabolism; D005644:alpha-L-Fucosidase / Q000378:metabolism
D007527:Isoenzymes; D009711:Nucleotides; D012794:Sialic Acids; D000509:alpha-Fetoproteins; D006154:Guanosine Diphosphate Fucose; D000255:Adenosine Triphosphate; D006602:Hexosyltransferases; D005644:alpha-L-Fucosidase; D005690:Galactose