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Glycobiology Advance Access published online on March 29, 2007
Glycobiology, doi:10.1093/glycob/cwm040
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© The Author 2007. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Biosynthesis and expression of the Sda and sialyl Lewis x antigens in normal and cancer colon

Nadia Malagolini1, Donatella Santini2, Mariella Chiricolo1 and Fabio Dall'Olio1,*

1 Dipartimento di Patologia Sperimentale, Via S. Giacomo 14, 40126, Bologna, Italy
2 Istituto di Anatomia e Istologia Patologica, Policlinico S. Orsola, Via Massarenti 9, 40100, Bologna, Italy

* Correspondence: Prof. Fabio Dall'Olio, Dipartimento di Patologia Sperimentale, Via S. Giacomo 14, 40126 Bologna, Italy. Phone: +390512094727, Fax: +390512094746, 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 a {alpha}2,3-sialylated type 2 chain: the first with a GalNAc ß1,4-linked to galactose, the second by a {alpha}1,3-linked fucose on GlcNAc. The Sda antigen is synthesised by Sda ß1,4-GalNAc transferase (ß4GalNAcT-II), which is downregulated in colon cancer, while sLex is a cancer-associated antigen. In view of the possible competition between ß4GalNAcT-II and the fucosyltransferases synthesising 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 relationship. 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 {alpha}1,3 fucosyltransferases on 3' sialyllactosamine parallels that of ß4GalNAcT-II and iii) both ß4GalNAcT-II and fucosyltransferase activities parallel sLex expression. Quantitative RT-PCR 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 fucosyltransferase 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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H.-R. Wang, C.-Y. Hsieh, Y.-C. Twu, and L.-C. Yu
Expression of the Human Sda -1,4-N-Acetylgalactosaminyltransferase II Gene is Dependent on the Promoter Methylation Status
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[Abstract] [Full Text] [PDF]


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