6′-Sulfo Sialyl Lex but Not 6-Sulfo Sialyl Lex Expressed on the Cell Surface Supports L-selectin-mediated Adhesion

Tsuboi, Shigeru; Isogai, Yukihiro; Hada, Noriyasu; King, Jennifer K.; Hindsgaul, Ole; Fukuda, Minoru

doi:10.1074/jbc.271.44.27213

Cited by 89 publications

(56 citation statements)

References 45 publications

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“…Furthermore, Kannagi and coworkers (33, 34) have described 6-sulfo-sLe X -reactive antibodies that stain HEVs and inhibit L-selectin binding to HEVs. With respect to the contribution of Gal-6-SO 4 , several groups have reported that this modification of sLe X or of sLe X mimetics either enhances or does not affect L-selectin binding (29,30,(35)(36)(37). In marked contrast, Feizi and co-workers found that this modification eliminates binding to L-selectin (28, 38).…”

Section: Sulfated Forms Of Sialyl-lementioning

confidence: 99%

Minimal Sulfated Carbohydrates for Recognition by L-selectin and the MECA-79 Antibody

Bruehl¹,

Bertozzi²,

Rosen³

2000

Journal of Biological Chemistry

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Sulfated forms of sialyl-LeX containing Gal-6-SO 4 or GlcNAc-6-SO 4 have been implicated as potential recognition determinants on high endothelial venule ligands for L-selectin. The optimal configuration of sulfate esters on the N-acetyllactosamine (Gal␤134GlcNAc) core of sulfosialyl-Le X , however, remains unsettled. Using a panel of sulfated lactose (Gal␤134Glc) neoglycolipids as substrates in direct binding assays, we found that 6,6-disulfolactose was the preferred structure for L-selectin, although significant binding to 6-and 6-sulfolactose was observed as well. Binding was EDTA-sensitive and blocked by L-selectin-specific monoclonal antibodies. Surprisingly, 6,6-disulfolactose was poorly recognized by MECA-79, a carbohydrate-and sulfate-dependent monoclonal antibody that binds competitively to L-selectin ligands. Instead, MECA-79 bound preferentially to 6-sulfolactose. The difference in preferred substrates between L-selectin and MECA-79 may explain the variable activity of MECA-79 as an inhibitor of lymphocyte adhesion to high endothelial venules in lymphoid organs. Our results suggest that both Gal-6-SO 4 and GlcNAc-6-SO 4 may contribute to L-selectin recognition, either as components of sulfosialyl-Le X capping groups or in internal structures. By contrast, only GlcNAc-6-SO 4 appears to contribute to MECA-79 binding. L-selectin, the "leukocyte selectin," mediates the tethering and rolling of lymphocytes along high endothelial venules (HEVs) 1 in peripheral lymph nodes, a prerequisite for extravasation of the lymphocytes (1-3). By virtue of a calcium-type lectin domain at its amino terminus, L-selectin functions as a calcium-dependent, carbohydrate-binding receptor that recognizes a set of discrete counter-receptors (generally termed ligands) displayed on the luminal aspect of HEVs (reviewed in Refs. 4 and 5). Several HEV-expressed, L-selectin-reactive ligands (all of which possess mucin-like domains) have been identified as potential physiological ligands for L-selectin (reviewed in Ref. 6). These include GlyCAM-1 (7), CD34 (8, 9), and podocalyxin (10).A large body of evidence has established that the optimal interaction between L-selectin and these HEV-expressed ligands requires sialylation, fucosylation, and carbohydrate sulfation (11)(12)(13)(14)(15)(16)(17). In an attempt to rationalize these requirements in terms of carbohydrate structures, a detailed analysis of the O-linked oligosaccharide side chains of GlyCAM-1 was conducted (18 -20). Sulfation analysis of acid-hydrolyzed glycans revealed monosulfated monosaccharides and disaccharides (Nacetyllactosamine) with equivalent levels of Gal-6-SO 4 and GlcNAc-6-SO 4 . Analysis of the simplest oligosaccharide side chains identified equivalent levels of two novel sulfated isomers of sialyl-Le X (sLe X ), 6Ј-sulfo-sLe X , containing Gal-6-SO 4 , and 6-sulfo-sLe X , containing GlcNAc-6-SO 4 (see Fig. 1), as capping groups of core-2 branched oligosaccharides. The finding of a sLe X motif was significant because this tetrasaccharide binds to all three sel...

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Section: Sulfated Forms Of Sialyl-lementioning

confidence: 99%

Minimal Sulfated Carbohydrates for Recognition by L-selectin and the MECA-79 Antibody

Bruehl¹,

Bertozzi²,

Rosen³

2000

Journal of Biological Chemistry

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“…Indeed, there are well-established examples of polypeptidespecific glycosylation reactions in other systems (70). An unusual 6 Ј -sulfated SLe x structure found on GlyCAM-1 (4, 11, 43) was initially thought to be a candidate; however, direct analysis of the chemically synthesized molecule indicates that it is not a particularly potent ligand in comparison with SLe x (71,72). A more promising candidate may be a relatively unusual Core 2 branched sialylated polyfucosylated O-linked chain found in a small copy number on PSGL-1 (32); however, this has not yet been directly shown to be essential for P-selectin recognition.…”

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confidence: 99%

Selectin ligands: will the real ones please stand up?

Varki¹

1997

J. Clin. Invest.

287

231

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“…In sulfated form, such as 6-sulfo sialyl Lewis X, sialic acid α2 3Galβ1 4[Fucα1 3(sulfo 6)] GlcNAc, this carbohydrate is present in unique vascular cells, high-endothelial (HEV) cells and is recognized by L-selectin in lymphocytes when lymphocytes are recruited to lymph nodes and endothelial cells expressed at chronic inflammatory sites. 4) Although an isomer of 6-sulfo sialyl Lewis X, 6′-sulfo sialyl Lewis X sulfo 6Galβ1 4 (Fucα1 3) GlcNAc was also proposed as a selectin ligand, 5) this was later excluded. This is because sulfation takes place before α1 3 fucosylation and α1,3-fucosyltransferase cannot add 6′-sulfated N-acetyllactosamine.…”

Section: Carbohydrates Ligands Need To Be Syn-thesizedmentioning

confidence: 99%

Recent Progress in Carbohydrate Biosynthesis and Function in Relation to Tumor Biology

Fukuda

2012

Biological & Pharmaceutical Bulletin

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Recent development in carbohydrate markers and functions are described. Identification of carbohydrate epitope for cancer-specific antibody is introduced. This novel approach involves the key glycosyltransferases that synthesize tumor-associated carbohydrate-antigens and elucidate the biosynthetic pathways. This is the true determination of carbohydrate ligands and glycan array is secondary to determine the epitope. Tumor suppressor activity of carbohydrate is described. Cell surface carbohydrate, which expressed in normal cells is diminished on cancer cells, function as a tumor suppressor. Glycans attached to α-dystroglycan function as laminin-binding glycans. In cancer cells, oncogene downregulates laminin-binding glycans and they do not bind to laminin in extracellular matrix, making cells to mobile. Thus, laminin-binding glycans function to suppress the cell mobility, thereby suppressing tumor formation in normal cells. This article summarizes the recent progress in the regulation of carbohydrate function in cancer cells. Since the review is short and not comprehensive, other several important topics may be missing.Key words cancer specific carbohydrate antigen; antibody epitope; glycosyltransferase CARBOHYDRATES LIGANDS NEED TO BE SYN-THESIZEDIn the past three decades, the changes in cell surface carbohydrates in malignant transformation showed that the changes can be classified as follows: 1) Carbohydrates that are substantially increased in cancer cells compared to parent untransformed cells, 2) carbohydrates that decreased in cancer cells compared to parent untransformed cells, and 3) carbohydrates that are essentially unchanged after oncogenic transformation. In these three different groups, studies on the first group have been extensively carried out. [1][2][3] In particular, the development of monoclonal antibodies specific to cancer cells has been very powerful in identifying carbohydrates that are enriched in cancer cells. By using these monoclonal antibodies, the expression of carbohydrates can be regarded as tumor-associated carbohydrate antigens.In early studies however, these carbohydrates were not necessarily discovered as carbohydrate antigens were highly expressed in cancer cells, but these carbohydrates are in subset of cells such as embryonic cells. In other cases, a subset of normal cells express those carbohydrate antigens and cancer cells express the same carbohydrates in increased amounts and the difference in the expression in normal and cancer cell is its quantity. One of such example is sialyl Lewis X that is present in neutrophils (granulocytes) in blood. Sialyl Lewis X present on neutrophils function as a selectin ligand in neutrophils recruitment to inflammatory sites. In sulfated form, such as 6-sulfo sialyl Lewis X, sialic acid α2 3Galβ1 4[Fucα1 3(sulfo 6)] GlcNAc, this carbohydrate is present in unique vascular cells, high-endothelial (HEV) cells and is recognized by L-selectin in lymphocytes when lymphocytes are recruited to lymph nodes and endothelial cells expressed at chron...

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6′-Sulfo Sialyl Lex but Not 6-Sulfo Sialyl Lex Expressed on the Cell Surface Supports L-selectin-mediated Adhesion

Cited by 89 publications

References 45 publications

Minimal Sulfated Carbohydrates for Recognition by L-selectin and the MECA-79 Antibody

Minimal Sulfated Carbohydrates for Recognition by L-selectin and the MECA-79 Antibody

Selectin ligands: will the real ones please stand up?

Recent Progress in Carbohydrate Biosynthesis and Function in Relation to Tumor Biology

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