The carbohydrate determinants Sda and sialyl Lewis x (sLex) both result from substitution of a alpha2,3-sialylated type 2 chain: the first with a GalNAc beta1,4-linked to galactose, the second by a alpha1,3-linked fucose on GlcNAc. The Sda antigen is synthesised by Sda beta1,4-GalNAc transferase (b4GalNAcT-II), which is downregulated in colon cancer, while sLex is a cancer-associated antigen. In view of the possible competition between b4GalNAcT-II and the fucosyltransferases synthesising the sLex antigen, we investigated whether b4GalNAcT-II acts as a negative regulator of sLex expression in colon cancer. b4GalNAcT-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 b4GalNAcT-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 alpha1,3 fucosyltransferases on 3' sialyllactosamine parallels that of beta4GalNAcT-II and iii) both beta4GalNAcT-II and fucosyltransferase activities parallel sLex expression. Quantitative RT-PCR analysis reveals that the transcripts of b4GalNAcT-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 b4GalNAcT-II can inhibit sLex expression in an experimental model although not in colon cancer tissues.
Biosynthesis and expression of the Sda and sialyl Lewis x antigens in normal and cancer colon / Malagolini N.; Santini D.; Chiricolo M.; Dall'Olio F.. - In: GLYCOBIOLOGY. - ISSN 0959-6658. - STAMPA. - 17:(2007), pp. 688-697. [10.1093/glycob/cwm040]
Biosynthesis and expression of the Sda and sialyl Lewis x antigens in normal and cancer colon
MALAGOLINI, NADIA;SANTINI, DONATELLA;CHIRICOLO, MARIELLA;DALL'OLIO, FABIO
2007
Abstract
The carbohydrate determinants Sda and sialyl Lewis x (sLex) both result from substitution of a alpha2,3-sialylated type 2 chain: the first with a GalNAc beta1,4-linked to galactose, the second by a alpha1,3-linked fucose on GlcNAc. The Sda antigen is synthesised by Sda beta1,4-GalNAc transferase (b4GalNAcT-II), which is downregulated in colon cancer, while sLex is a cancer-associated antigen. In view of the possible competition between b4GalNAcT-II and the fucosyltransferases synthesising the sLex antigen, we investigated whether b4GalNAcT-II acts as a negative regulator of sLex expression in colon cancer. b4GalNAcT-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 b4GalNAcT-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 alpha1,3 fucosyltransferases on 3' sialyllactosamine parallels that of beta4GalNAcT-II and iii) both beta4GalNAcT-II and fucosyltransferase activities parallel sLex expression. Quantitative RT-PCR analysis reveals that the transcripts of b4GalNAcT-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 b4GalNAcT-II can inhibit sLex expression in an experimental model although not in colon cancer tissues.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.