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.
Malagolini N., Santini D., Chiricolo M., Dall'Olio F. (2007). Biosynthesis and expression of the Sda and sialyl Lewis x antigens in normal and cancer colon. GLYCOBIOLOGY, 17, 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.
