Glycobiology Advance Access originally published online on March 29, 2007
Glycobiology 2007 17(7):688-697; doi:10.1093/glycob/cwm040
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Biosynthesis and expression of the Sda and sialyl Lewis x antigens in normal and cancer colon
2 Dipartimento di Patologia Sperimentale, Via S. Giacomo 14, 40126 Bologna, Italy
3 Istituto di Anatomia e Istologia Patologica, Policlinico S. Orsola, Via Massarenti 9, 40100 Bologna, Italy
1 To whom correspondence should be addressed; Tel: +39 0512094727; Fax: +39 0512094746; e-mail: fabio.dallolio{at}unibo.it
Received on July 14, 2006; revised on March 22, 2007; accepted on March 25, 2007
The carbohydrate determinants Sda and sialyl Lewis x (sLex) both result from substitution of an 
2,3-sialylated type 2 chain: the first with an N-acetylgalactosamine (GalNAc) ß1,4-linked to Gal and the second by an 1,3-linked fucose on N-acetylglucosamine. The Sda antigen is synthesized by Sda ß1,4-N-acetylgalactosaminyltransferase II (ß4GalNAcT-II), which is downregulated in colon cancer, whereas sLex is a cancer-associated antigen. In view of the possible competition between ß4GalNAcT-II and the fucosyltransferases (FucTs) synthesizing the sLex antigen, we investigated whether ß4GalNAcT-II acts as a negative regulator of sLex expression in colon cancer. ß4GalNAcT-II cDNA, when expressed in LS174T colon cancer cells, induces the expression of the Sda antigen, a dramatic inhibition of sLex expression on cell membranes, and the replacement of sLex with the Sda antigen on 290 kDa glycoproteins. Unexpectedly, in colorectal cancer specimens, ß4GalNAcT-II and sLex show a direct relation. The reasons appear to be (i) Sda and sLex antigens are expressed by different glycoproteins of 340 and 290 kDa, respectively; (ii) the activity of 1,3-FucTs on 3'-sialyllactosamine parallels that of ß4GalNAcT-II; and (iii) both ß4GalNAcT-II and FucT activities parallel sLex expression. Quantitative reverse transcription–polymerase chain reaction analysis reveals that the transcripts of ß4GalNAcT-II and those of FucT-III and FucT-VII are positively correlated. These data indicate that in colon cancer tissues, the sLex antigen is regulated mainly by the total FucT activity on 3'-sialyllactosamine acceptors and that ß4GalNAcT-II can inhibit sLex expression in an experimental model, although not in colon cancer tissues.
Key words: N-acetylgalactosaminyltransferase / fucosyltransferases / Sda antigen / sialyl Lewis x antigen / colon cancer
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