A novel disialoganglioside (IV3NeuAcIII6NeuAcLc4) of human adenocarcinoma and the monoclonal antibody (FH9) defining this disialosyl structure

Fukushi, Yasuo; Nudelman, Edward; Levery, Steven B.; Higuchi, Tetsuo; Hakomori, Sen‐itiroh

doi:10.1021/bi00358a018

Cited by 70 publications

(32 citation statements)

References 42 publications

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“…Composition analysis of glycosphingolipids in renal cancers revealed increased gangliosides in some cases [41]. Fukushi et al [42] reported the expression of disialyl Lc4 in many tumour cells based on studies using a specific mAb. This structure was first defined by Smith and Ginsburg [43].…”

Section: Discussionmentioning

confidence: 99%

Identification and expression of a sialyltransferase responsible for the synthesis of disialylgalactosylgloboside in normal and malignant kidney cells: downregulation of ST6GalNAc VI in renal cancers

Senda

Itoh

Tsuchida

et al. 2007

Biochemical Journal

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Although disialyl glycosphingolipids such as GD3 and GD2 have been considered to be associated with malignant tumours, whether branched-type disialyl glycosphingolipids show such an association is not well understood. We investigated the sialyltransferases responsible for the biosynthesis of DSGG (disialylgalactosylgloboside) from MSGG (monosialylgalactosylgloboside). Among six GalNAc:α2,6-sialyltransferases cloned to date, we focused on ST6GalNAc III, V and VI, which utilize sialylglycolipids as substrates. In vitro enzyme analyses revealed that ST6GalNAc III and VI generated DSGG from MSGG with V max /K m values of 1.91 and 4.16 respectively. Transfection of the cDNA expression vectors for these enzymes resulted in DSGG expression in a renal cancer cell line. Although both ST6GalNAc III and VI genes were expressed in normal kidney cells, the expression profiles of ST6GalNAc VI among 20 renal cancer cell lines correlated clearly with those of DSGG, suggesting that the sialyltransferase involved in the synthesis of DSGG in the kidney is ST6GalNAc-VI. ST6GalNAc-VI and DSGG were found in proximal tubule epithelial cells in normal kidney tissues, while they were downregulated in renal cancer cell lines and cancer tissues. All these findings indicated that DSGG was suppressed during the malignant transformation of the proximal tubules as a maturation arrest of glycosylation.

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Section: Discussionmentioning

confidence: 99%

Identification and expression of a sialyltransferase responsible for the synthesis of disialylgalactosylgloboside in normal and malignant kidney cells: downregulation of ST6GalNAc VI in renal cancers

Senda

Itoh

Tsuchida

et al. 2007

Biochemical Journal

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“…The R f values of gangliosides designated doublet band 3, band 4, and band 6 were similar to those of the sialosyl K2C6-lacto-neotetraosylceramide (IV 6 NeuAcnLc 4 ) doublet, sialosyl K2C3-lacto-norhexaosylceramide (VI 3 NeuAcnLc 6 ), and sialosyl K2C6-lacto-norhexaosylceramide (VI 6 NeuAcnLc 6 ) of human erythrocytes respectively. The presence of the IV 6 NeuAcnLc 4 doublet and VI 6 NeuAcnLc 6 in human colonic adenocarcinoma has been reported [7,12]. During NaBT-induced di¡erentiation of HCT 116 cells, G M3 , G M2 , and unidenti¢ed bands 5 and 7 increased appreciably while ganglioside corresponding to VI 3 NeuAcnLc 6 decreased.…”

Section: Di¡erentiation-related Changes In Ganglioside Pattern Ofmentioning

confidence: 94%

Induction of terminal differentiation and apoptosis in human colonic carcinoma cells by brefeldin A, a drug affecting ganglioside biosynthesis

et al. 1999

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An appreciable increase in G M3 with a concomitant decrease in some neolacto-series gangliosides was observed during differentiation of human colonic carcinoma HCT 116 cells induced by a differentiating agent. When the cells were treated with brefeldin A (BFA), a striking increase in de novo biosynthesis of G M3 and a decrease in biosynthesis of neolactoseries gangliosides were observed after 6 h. Clear morphological changes to differentiated epithelial cells and an arrest of cells in the G 0 /G 1 phase of the cell cycle were observed after 1 day of treatment. Then the cells were led to apoptosis. This activity was not affected by forskolin, which antagonizes the effects of BFA on protein transport and the Golgi apparatus. These results suggest that the differentiation-inducing activity of BFA might be due to its modulatory effect on ganglioside biosynthesis, and that a specific change in ganglioside pattern is an essential prerequisite for induction of differentiation, providing a novel target for differentiation therapy of cancer.z 1999 Federation of European Biochemical Societies.

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“…The glycolipid SdiLex (27), previously shown to be an inhibitor of ELAM-1 (6), incorporates both the SLex and CD65 structures (see Fig. 5).…”

Section: Cd65mentioning

confidence: 98%

CD62 and endothelial cell-leukocyte adhesion molecule 1 (ELAM-1) recognize the same carbohydrate ligand, sialyl-Lewis x.

Polley

Phillips

Wayner

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

470

168

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The leukocyte receptor CD62, which is expressed on activated platelets and endothelial cells, is shown to mediate cell adhesion by binding a sialylated carbohydrate structure, sialyl-Lewis x, found on neutrophils, monocytes, and tumor cells. This structure has previously been identified as the ligand for another member of the LEC-CAM family of cell adhesion molecules, endothelial cell-eukocyte adhesion molecule 1, which also binds neutrophils and monocytes. The results demonstrate that although the two LEC-CAMs differ in their biological activities by their distribution and mode of expression, they are capable of mediating cell adhesion by recognition of the same carbohydrate ligand.Leukocyte trafficking and recruitment to sites of inflammation are mediated by three adhesion receptor families, the integrin and immunoglobulin superfamilies and the recently described LEC-CAM, or selectin family (1)(2)(3)(4) (100 nm) (13). Neutrophils were isolated from fresh human blood by centrifugation at room temperature through mono-poly resolving medium (Flow Laboratories) followed by three washes in ice-cold Hanks' balanced salt solution (GIBCO) containing 20 mM Hepes (GIBCO) and 0.2% glucose (Fisher). Human umbilical vein endothelial cells were obtained as described (6). HL-60 cells were cultured in RPMI 1640 containing 10%6 fetal calf serum. Chinese hamster ovary (CHO-Ki) cells, glycosylation mutants , and the carcinoma line were cultured in the a modification of Eagle's minimal essential medium (a-MEM) containing ribonucleosides, deoxyribonucleosides, and 10%1o fetal calf serum.Assays for CD62-Mediated Adhesion to Activated Platelets. Two assays were used, a fluid phase assay and a plate assay. The fluid phase assay (see Figs. 2-4) was performed essentially as described (10) for PADGEM (CD62). Platelets at 2 x 108 per ml were activated with thrombin at 0.25 units/ml for 20 min at room temperature without stirring. Twenty microliters of the activated platelet suspension was then mixed with an equal volume ofa suspension ofthe cells (2 x 106 cells per ml) to be assessed for adhesion. Adhesion was evaluated microscopically and was scored as the percent ofthe test cells that had bound two or more platelets. The plate assay used was a modification of the endothelial cell-neutrophil adherence assay previously described (20). A suspension of platelets (300 ,l) at 108 per ml was applied to each well of a 48-well plate that had previously been coated with 0.1% gelatin. The Gal431-4 GlcNAc / FUCCY1 3 Le' Abbreviations: LEC-CAM, a family of cell adhesion molecules, each of which contains an N-terminal lectin domain followed by an epidermal growth factor-like domain and a series of consensus repeats similar to those found in complement regulatory proteins; ELAM-1, endothelial cell-leukocyte adhesion molecule

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A novel disialoganglioside (IV3NeuAcIII6NeuAcLc4) of human adenocarcinoma and the monoclonal antibody (FH9) defining this disialosyl structure

Cited by 70 publications

References 42 publications

Identification and expression of a sialyltransferase responsible for the synthesis of disialylgalactosylgloboside in normal and malignant kidney cells: downregulation of ST6GalNAc VI in renal cancers

Identification and expression of a sialyltransferase responsible for the synthesis of disialylgalactosylgloboside in normal and malignant kidney cells: downregulation of ST6GalNAc VI in renal cancers

Induction of terminal differentiation and apoptosis in human colonic carcinoma cells by brefeldin A, a drug affecting ganglioside biosynthesis

CD62 and endothelial cell-leukocyte adhesion molecule 1 (ELAM-1) recognize the same carbohydrate ligand, sialyl-Lewis x.

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