The addition of sialic acid in alpha2,6-linkage to lactosaminic termini of glycoproteins is mainly mediated by beta-galactoside alpha2,6 sialyltransferase (ST6Gal.I). This enzyme and its cognate oligosaccharide structure are frequently overexpressed in cancer and are associated with increased malignancy but the cellular and molecular bases of this relationship are not clear. In this study, we have investigated the role of ST6Gal.I in the in vivo growth. First, we have xenografted in nude mice colon cancer cell lines and analyzed the expression of ST6Gal.I and of alpha2,6-sialylated sugar chains in the xenograft-derived (XD) cell lines. Compared with parental cell lines, the XD cell lines express dramatically increased levels of ST6Gal.I mRNA, detected by RT-PCR analysis, and enzyme activity, as well as an increased reactivity with the alpha2,6-sialyl-specific lectin from Sambucus nigra (SNA) suggesting either a selection of the cells expressing higher levels of ST6Gal.I. Then, we investigated the in vivo growth of clones derived from transfection with the ST6Gal.I cDNA of the colon cancer cell line SW48, which was originally devoid of ST6Gal.I expression. Compared with mock-transfectants, ST6Gal.I-transfectants form more rapidly growing tumours. Moreover, when an identical number of mock- and ST6Gal.I-transfected cells was mixed and injected in the nude mice, the xenografts and the xenograft-derived cell lines were comprised only of SNA-positive ST6Gal.I-transfectants, while mock-transfected cells were usually not present in the xenograft. These results indicate that during the growth of the tumour the cells expressing high levels of alpha2,6-sialylated glycoconjugates are positively selected because of a growth advantage.
In vivo growth advantage of colon cancer cell lines expressing beta-galactoside alpha 2,6 sialyltransferase (ST6Gal.I)
DALL'OLIO, FABIO;MALAGOLINI, NADIA;CHIRICOLO, MARIELLA
2005
Abstract
The addition of sialic acid in alpha2,6-linkage to lactosaminic termini of glycoproteins is mainly mediated by beta-galactoside alpha2,6 sialyltransferase (ST6Gal.I). This enzyme and its cognate oligosaccharide structure are frequently overexpressed in cancer and are associated with increased malignancy but the cellular and molecular bases of this relationship are not clear. In this study, we have investigated the role of ST6Gal.I in the in vivo growth. First, we have xenografted in nude mice colon cancer cell lines and analyzed the expression of ST6Gal.I and of alpha2,6-sialylated sugar chains in the xenograft-derived (XD) cell lines. Compared with parental cell lines, the XD cell lines express dramatically increased levels of ST6Gal.I mRNA, detected by RT-PCR analysis, and enzyme activity, as well as an increased reactivity with the alpha2,6-sialyl-specific lectin from Sambucus nigra (SNA) suggesting either a selection of the cells expressing higher levels of ST6Gal.I. Then, we investigated the in vivo growth of clones derived from transfection with the ST6Gal.I cDNA of the colon cancer cell line SW48, which was originally devoid of ST6Gal.I expression. Compared with mock-transfectants, ST6Gal.I-transfectants form more rapidly growing tumours. Moreover, when an identical number of mock- and ST6Gal.I-transfected cells was mixed and injected in the nude mice, the xenografts and the xenograft-derived cell lines were comprised only of SNA-positive ST6Gal.I-transfectants, while mock-transfected cells were usually not present in the xenograft. These results indicate that during the growth of the tumour the cells expressing high levels of alpha2,6-sialylated glycoconjugates are positively selected because of a growth advantage.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
