Possible Role of Human Natural Anti-Gal Antibodies in the Natural Antitumor Defense System

Castronovo, Vincent; Colin, Claude; Parent, Bernadette; Foidart, Jean-Michel; Lambotte, R; Mahieu, P.

doi:10.1093/jnci/81.3.212

Cited by 66 publications

(23 citation statements)

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“…Penno and colleagues (19) have shown that terminal galactosylation of a 110-kDa cell-surface glycoprotein is correlated with invasiveness of murine adrenal carcinoma cells and their adherence to LN. In human models, adhesion of breast cancer cell lines to LN or to human umbilical vein was inhibited by antibodies against aGal(1-3)Gal structures (20). Our results suggest a possible molecular mechanism for the interaction between LN and integrin based on recognition of receptor a-galactosyl residues.…”

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confidence: 68%

Functionally distinct roles for glycosylation of alpha and beta integrin chains in cell-matrix interactions.

Chammas

Veiga

Travassos

et al. 1993

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

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Laminin interaction with gpl20/140, a B16-F10 laminin-binding protein immunologically related to a6p1integrin, has been shown to be dependent on oligosaccharides from both ligand and receptor. Lectin analysis of gpl20/140 led to the conclusion that this integrin is a sialoglycoprotein bearing mainly complex antennary structures. By means of exoglycosidase treatment, it was possible to identify a-galactosyl residues on the integrin a chain as the laminin-binding determinants. These residues are involved in cell adhesion to laminin. On the other hand, (3-chain complex antennary structures, whose synthesis could be inhibited by swainsonine, were associated with cell spreading rather than cell adhesion. Thus, it was possible to modulate integrin-mediated ceOl adhesion and spreading through changes in the glycosylation state of integrin a and ( chains.Cell-matrix interactions are mediated by integrin and nonintegrin receptors (1). Integrins are heterodimeric glycoproteins consisting of two subunits, a and ,B. Combinations of two such polypeptides lead to the formation of different receptors, presenting different ligand specificities. Although the molecular basis of the integrin-ligand interaction is not completely understood, some experimental evidence suggests that posttranslational events are important determining factors (2). In a previous report (3), we characterized the binding of laminin-nidogen complex (LN) to gpl20/140, a LN-binding integrin from B16-F1O melanoma cells, as dependent on asparagine-linked oligosaccharides from both interactants. In the present study, we report on the further characterization of the oligosaccharide chains of affinity-purified gpl20/140 based on its reactivity with a panel of lectins. We have evaluated the functional role of the sugar residues present in the integrin molecule in cell-matrix interactions. A suggestion is made of probable carbohydrate residues involved in adhesion to or spreading of B16-F1O cells on LN surfaces.EXPERIMENTAL PROCEDURES Cell Culture. Murine melanoma cells (B16-F10 line), a gift from M. Hendrix (University of Arizona), were maintained in tissue culture flasks with RPMI 1640 medium (Sigma), supplemented with 10% heat-inactivated fetal calf serum (Cultilab, Campinas, Brazil) [3H]leucine uptake) and displayed no effect on cell viability, as determined by trypan blue exclusion.

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confidence: 68%

Functionally distinct roles for glycosylation of alpha and beta integrin chains in cell-matrix interactions.

Chammas

Veiga

Travassos

et al. 1993

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

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“…For example, they can influence the three-dimensional structure and function of glycoproteins [Sairam and Jiang, 1992], decrease the protease susceptibility of some glycoproteins [Varki, 1993], serve as ligands for mammalian lectins [Zhou and Cummings, 1992] and contribute to cell-cell [Lowe, 1994] and cell-extracellular matrix interactions [Carson, 1992]. When expressed aberrantly on cancer cells, complex carbohydrates have been shown to modulate tumor cell adhesion [Olden, 1993], influence host anti-tumor immunity [Dennis and Laferté, 1985;Castronovo et al, 1989], and contribute to the malignant behavior of these cells [Dennis, 1992]. Specific examples of colon cancer-associated glycosylation changes include aberrant expression of ABH and Lewis (Le) blood group antigens [Hakomori and Kannagi, 1983;Coon and Weinstein, 1986;Hoff et al, 1989;Bloom et al, 1990], increased sialylation and fucosylation of type 1 (Gal␤1-3GlcNAc␤-R) and type 2 (Gal␤1-4GlcNAc␤-R) chains [Hakomori and Kannagi, 1983], increased expression of poly-N-acetyllactosamine structures (i.e., repeating type 2 chains) [Saitoh et al, 1992], alterations in O-linked oligosaccharides of colonic mucins [Kannagi et al, 1986;Baeckstrom et al, 1991;Fernandes et al, 1991], and increased branching of N-linked oligosaccharides [Fernandes et al, 1991;Saitoh et al, 1992], in particular initiation of the ␤1-6 antenna by GlcNAc T-V [Dennis et al, 1987;Dennis, 1992].…”

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confidence: 99%

Integrin ?3?1 expressed by human colon cancer cells is a major carrier of oncodevelopmental carbohydrate epitopes

et al. 1999

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Oncodevelopmental carbohydrate epitopes are a common feature of human colorectal carcinoma, yet their biological significance remains unclear. We have shown previously that monoclonal antibody (MAb) 3A7, which recognizes a determinant on type 2 chain blood group A and B oligosaccharides, detects oncodevelopmental changes in azoxymethane-induced rat colon tumors and some human colon cancer cell lines. (Laferté S et al. [19951 J. Cell. Biochem. 57:101-119). In this study, we set out to purify gp140, the major glycoprotein carrier of the 3A7 epitope expressed by human colon cancer cells, as a first step towards elucidating the contribution of the 3A7 epitope and its major glycoprotein carrier to colon cancer progression. To this end, gp140 was purified from HT29 cells and used for the preparation of polypeptide-specific monoclonal antibodies. Five monoclonal antibodies (7A8, 7B11, 8C7, 8H7, and 11D4) immunoprecipitated a 3A7-immunoreactive glycoprotein complex of 140 kDa which was subsequently identified by partial protein sequencing as alpha3beta1 integrin. Flow cytometric analysis of Chinese hamster ovary (CHO) cells expressing different human integrin chains revealed that MAbs 7A8 and 7B11 detect the alpha3 integrin subunit whereas MAbs 8C7 and 8H7 detect the beta1 integrin subunit. MAb 11D4, which did not bind to any of the CHO transfectants, detected type 2 chain blood group A determinant. Flow cytometric analysis of a panel of human colon carcinoma cell lines obtained from blood group A, AB, or B individuals revealed a direct correlation between cell-surface expression of the 3A7 epitope and alpha3 integrin subunit, suggesting that alpha3beta1 integrin is a preferred target of the 3A7 epitope in colon cancer cells. Using lectins and glycosidases to examine further the carbohydrate structure of alpha3beta1 integrin, we demonstrated that it is a sialoglycoprotein containing both N- and O-linked oligosaccharides. In addition, both alpha3 and beta1 integrin subunits express beta1-6 branched Asn-linked oligosaccharides and short poly-N-acetyllactosamine units (Galbeta1-4GlcNAc-R; n < or = 3), glycans previously implicated in cancer metastasis.Thus, alpha3beta1 integrin expressed by human colon carcinoma cells is a major carrier of oncodevelopmental carbohydrate epitopes whose presence may modulate tumor cell adhesion, migration, and/or invasion.

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“…We also obtained evidence for specific anti-Forssman antibodies in human serum as a separate entity with only little cross-reactivity to anti-TF·-PAA antibodies. The ßD-Gal antibodies detected in human serum in our study should not be confused with the so-called 'anti-·Gal' antibodies [29][30][31].…”

Section: Discussionmentioning

confidence: 57%

Isolation and Characterization of Thomsen-Friedenreich-Specific Antibodies from Human Serum

Butschak

Karsten²

2002

Tumor Biol

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The Thomsen-Friedenreich (TF) disaccharide, galactose (Gal)β1–3GalNAcα-, is a blood group-related oncofetal antigen with remarkable tumor specificity. Postpartum, carbohydrate structures on the cell walls of the gastrointestinal flora evoke natural antibodies of presumed TF specificity. These antibodies may provide an early barrier against TF-carrying tumor cells. Their possible role, however, has been difficult to assess, since so far only a multivalent immunosorbent, asialoglycophorin (aGP), has been employed for their preparation, and therefore their fine specificities have been only insufficiently defined. We have used a novel immunosorbent consisting of synthetic TFα disaccharides (Galβ1–3GalNAcα-) coupled to polyacrylamide (PAA), which itself was covalently bound to cross-linked sepharose. For specificity analyses, aGP and a panel of PAA-conjugated mono- and oligosaccharides were employed. Binding to the PAA moiety was excluded. The affinity-purified anti-TFα antibodies were of the IgM (≧0.5 mg/100 ml of serum) and IgG (approximately 0.05 mg/100 ml of serum) classes. They did partially cross-react with TFβ, although we detected a second group of anti-TFβ antibodies (both IgM and IgG) which did not cross-react with TFα. The affinity-purified TFα antibodies showed only marginal cross-reactivity with the related antigens lactose, Gal, Tn or the Forssman antigen. Besides TF-specific antibodies, we found antibodies to the carbohydrate antigens Tn, Forssman and β-D-Gal as well as to noncarbohydrate epitopes of glycophorin in human serum.

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Possible Role of Human Natural Anti-Gal Antibodies in the Natural Antitumor Defense System

Cited by 66 publications

References 0 publications

Functionally distinct roles for glycosylation of alpha and beta integrin chains in cell-matrix interactions.

Functionally distinct roles for glycosylation of alpha and beta integrin chains in cell-matrix interactions.

Integrin ?3?1 expressed by human colon cancer cells is a major carrier of oncodevelopmental carbohydrate epitopes

Isolation and Characterization of Thomsen-Friedenreich-Specific Antibodies from Human Serum

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