Expression of α2,6-sialic acid-containing and Lewis-active glycolipids in several types of human ovarian carcinomas

Abstract

Abstract.To identify glycolipid antigens associated with histologically defined types of ovarian carcinomas, we determined the amounts of α2,6-sialyl and Lewis-active glycolipids, the specific activities of the α2,3-and α2,6-sialyltransferases, and the gene expression of sugar transferases in mucinous and serous cystadenocarcinoma, clear cell adenocarcinoma and endometrioid carcinoma tissues and cell lines derived from them. α2,6-sialyl glycolipid IV 6 NeuAcα-nLc 4 Cer detected with a newly developed monoclonal antibody, Y916, was present in 5/7 serous cystadenocarcinoma cases in relatively higher amounts than those in the other carcinoma tissues. On the other hand, the amounts of Lewis-active glycolipids in serous cystadenocarcinoma tissues were lower than those in the other carcinoma tissues. No correlation was observed between the structures of Lewis glycolipids and the histological classification. The gene expression of α2,3-and α2,6-sialyltransferases and α1,3/4-fucosyltransferase for the synthesis of Lewis-active glycolipids was not positively correlated with the amounts of the respective glycolipids, probably due to the epigenetic regulation of transferases in the overall metabolic pathways for lacto-series glycolipids. However, the amounts of GM3 and GD3 with short carbohydrate chains correlated with the relative intensities of GM3 and GD3 synthase gene expression, respectively. Among ovarian carcinoma-derived cell lines, the serous cystadenocarcinoma-derived ones exhibited a lower frequency of Lewis-active glycolipid expression than the other carcinoma-derived ones, which was similar to that in the respective tissues. Thus, malignancy-related Lewisactive glycolipids were shown to be regulated in different modes in ovarian serous cystadenocarcinomas and the other carcinomas.

Molecular Recognition Insights of Sialic Acid Glycans by Distinct Receptors Unveiled by NMR and Molecular Modeling

“…The sialoglycans with an α2-6-linked Neu5Ac to a Gal, a GalNAc, or GlcNAc residue are less common than the α2-3-linked counterparts. Nevertheless, in cancer cells, some of these types of linkages become more prominent and can be found as terminal motifs of N -/ O -glycans, as well as in glycolipids ( Tanaka et al, 2010 ; Varki et al, 2015 ). In contrast to the α2-3 sialoglycans, the α2-6 ones do not suffer further modifications.…”

Evaluation of a glycoengineered monoclonal antibody via LC-MS analysis in combination with multiple enzymatic digestion

“…Terminal α2,6-sialylation could also be important for antibody efficacy. 19 It has been found that terminal α2,6-sialylation of Fc glycans plays a critical role for the anti-inflammatory activity of human intravenous immunoglobulins, while terminal α2,3-sialylation did not have anti-inflammatory activity. 20 This discovery underscores the importance of α2,6-sialylation on the antibody glycans.…”