Summary and conclusion
Lex (α1→3 fucosylated type 2 chain) functions as an adhesion molecule capable of Ca2+-mediated homotypic binding. Cells with high surface expression of Lex therefore exhibit strong self-aggregation (based on Lex-Lex interaction) in the presence of Ca2+. In this review, I have summarized several lines of supporting data for this concept, and the role of Lex-Lex interaction in the process of embryo compaction and autoaggregation of F9 teratocarcinoma cells. In general, cell adhesion events based on Lex-Lex interaction may be followed and reinforced by integrin- or Ig receptor-based adhesion systems.
SLex, the 2→3 sialosyl derivative of Lex, and its positional isomer SLea, have been identified as the target molecules for selectin-dependent cell adhesion. Adhesion of leukocytes or tumour cells to ECs or platelets, which express E-selectin and P-selectin respectively, is initiated by this process. The target epitopes SLex and SLea are presented mainly on transmembrane glycoproteins having many clusters of O-linked carbohydrate chains. Therefore, inhibition of O-glycosylation may be effective for blocking selectin-mediated cell adhesion. The abundant presence of Lex epitope in the central nervous system, and the physiological changes of Lex expression as described in this monograph, reflect the adhesive properties of this molecule and its sialyosylated and/or fucosylated derivatives.
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References
Abe, K., McKibbin, J. M. &Hakomori, S. (1983). The monoclonal antibody directed to difucosylated type 2 chain (Fucα1→2Galβ1→4[Fucα1→3]GlcNAc; Y determinant).J. Biol. Chem. 258, 11 793–7.
Berg, E. L., Robinson, M. K., Mansson, O., Butcher, E. C. &Magnani, J. L. (1991) A carbohydrate domain common to both sialyl Lea and sialyl Lex is recognized by the endothelial cell leukocyte adhesion molecule ELAM-1.J. Biol. Chem. 266, 14 869–72.
Brown, A., Feizi, T., Gooi, H. C., Embleton, M. J., Picard, J. K. &Baldwin, R. W. (1983) A monoclonal antibody against human colonic adenoma recognizes difucosylated type 2 blood group chains.Biosci. Rep. 3, 163–70.
Eggens, I., Fenderson, B. A., Toyokuni, T., Dean, B., Stroud, M. R. &Hakomori, S. (1989) Specific interaction between Lex and Lex determinants: a possible basis for cell recognition in preimplantation embryos and in embryonal carcinoma cells.J. Biol. Chem. 264, 9476–84.
Fenderson, B. A., Zehavi, U. &Hakomori, S. (1984) A multivalent lacto-N-fucopentaose III-lysyllysine conjugate decompacts preimplantation mouse embryos, while the free oligosaccharide is ineffective.J. Exp. Med. 160, 1591–6.
Fenderson, B. A., Kojima, N., Stroud, M. R., Zhu, Z. &Hakomori, S. (1991) Specific interaction between Ley and H as a possible basis for trophectoderm-endometrium recognition during implantation [abstract 8.5].Glycoconjugate J. 8, 179.
Fukushi, Y., Nudelman, E. D., Levery, S. B., Rauvala, H. &Hakomori, S. (1984) Novel fucolipids accumulating in human cancer: III. A hybridoma antibody (FH6) defining a human cancer-associated difucoganglioside (VI3NeuAcV3III3Fuc2-nLc6).J. Biol. Chem. 259, 511–7.
Gooi, H. C., Feizi, T., Kapadia, A., Knowles, B. B., Solter, D. &Evans, M. J. (1981) Stage-specific embryonic antigen involves α1→3 fucosylated type 2 blood group chains.Nature 292, 156–8.
Hakomori, S. (1989). Aberrant glycosylation in tumors and tumor-associated carbohydrate antigens.Adv. Cancer Res. 52, 257–331.
Hakomori, S. (1991a) Carbohydrate-carbohydrate interaction as an initial step in cell recognition.Pure Appl. Chem. 63, 473–82.
Hakomori, S. (1991b) Possible new directions in cancer therapy based on aberrant expression of glycosphingolipids: anti-adhesion and ortho-signaling therapy.Cancer Cells 3, 461–70.
Hakomori, S., Nudelman, E. D., Levery, S. B., Solter, D. &Knowles, B. B. (1981) The hapten structure of a developmentally regulated glycolipid antigen (SSEA-1) isolated from human erythrocytes and adenocarcinoma: a preliminary note.Biochem. Biophys. Res. Commun. 100, 1578–86.
Hakomori, S., Nudelman, E. D., Levery, S. B. &Kannagi, R. (1984) Novel fucolipids accumulating in human adenocarcinoma: I. Glycolipids with di- or trifucosylated type 2 chain.J. Biol. Chem. 259, 4672–80.
Handa, K., Nudelman, E. D., Stroud, M. R., Shiozawa, T. &Hakomori, S. (1991) Selectin GMP-140 (CD62; PADGEM) binds to sialosyl-Lea and sialosyl-Lex, and sulfated glycans modulate this binding.Biochem. Biophys. Res. Commun. 181, 1223–30.
Kaizu, T., Levery, S. B., Nudelman, E. D., Stenkamp, R. E. &Hakomori, S. (1986) Novel fucolipids of human adenocarcinoma: monoclonal antibody specific for trifucosyl Ley (III3FucV3FucVI2FucnLc6), and a possible three-dimensional epitope structure.J. Biol. Chem. 261, 11 254–8.
Kojima, N., Handa, K., Newman, W. &Hakomori, S. (1992) Inhibition of selectin-dependent tumor cell adhesion to endothelial cells and platelets by blockingO-glycosylation of these cells.Biochem. Biophys. Res. Commun. 182, 1288–95.
Lloyd, K. O., Larson, G., Stromberg, N., Thurin, J. &Karlsson, K.-A. (1983). Mouse monoclonal antibody F-3 recognizes the difucosyl Type 2 blood group structure.Immunogenetics 17, 537–41.
Okoshi, H., Hakomori, S., Nisar, M., Zhou, Q., Kimura, S., Tashiro, K. &Igarashi, Y. (1991) Cell membrane signaling as target in cancer therapy II: inhibitory effect ofN,N,N-trimethylsphingosine on metastatic potential of murine B16 melanoma cell line through blocking of tumor cell-dependent platelet aggregation.Cancer Res. 51, 6019–24.
Phillips, M. L., Nudelman, E. D., Gaeta, F. C. A., Perez, M., Singhal, A. K., Hakomori, S. &Paulson, J. C. (1990) ELAM-1 mediates cell adhesion by recognition of a carbohydrate ligand, sialyl-Lex.Science 250, 1130–2.
Polley, M. J., Phillips, M. L., Wayner, E. A., Nudelman, E. D., Singhal, A. K., Hakomori, S. &Paulson, J. C. (1991) CD62 and endothelial cell-leukocyte adhesion molecule 1 (ELAM-1) recognize the same carbohydrate ligand, sialyl-Lewis x.Proc. Natl Acad. Sci. USA 88, 6224–8.
Solter, D. &Knowles, B. B. (1978) Monoclonal antibody defining a stage-specific mouse embryonic antigen (SSEA-1).Proc. Natl Acad. Sci. USA 75, 5565–9.
Springer, T. A. &Lasky, L. A. (1991) Sticky sugars for selectins.Nature 349, 196–7.
Stroud, M. R., Levery, S. B., Nudelman, E. D., Salyan, M. E. K., Towell, J. A., Roberts, C. E., Watanabe, M. &Hakomori, S. (1991) Extended type 1 chain glycosphingolipids: Dimeric Lea (III4V4Fuc2Lc6) as human tumor-associated antigen.J. Biol. Chem. 266, 8439–46.
Stroud, M. R., Levery, S. B., Salyan, M. E. K., Roberts, C. E. &Hakomori, S. (1992) Extended type-1 chain glycosphingolipid antigens: isolation and characterization of trifucosyl-Leb antigen (III4V4VI2Fuc3Lc6).Eur. J. Biochem. 203, 577–86.
Takada, A., Ohmori, K., Takahashi, N., Tsuyuoka, K., Yago, A., Zenita, K., Hasegawa, A. &Kannagi, R. (1991) Adhesion of human cancer cells to vascular endothelium mediated by a carbohydrate antigen, sialyl Lewis.A. Biochem. Biophys. Res. Commun. 179, 713–9.
Watanabe, M., Ohishi, T., Kuzuoka, M., Nudelman, E. D., Stroud, M. R., Kubota, T., Kodaira, S., Abe, O., Hirohashi, S., Shimosato, Y. &Hakomori, S. (1991)In vitro andin vivo antitumor effects of murine monoclonal antibody NCC-ST-421 reacting with dimeric Lea (Lea/Lea) epitope.Cancer Res. 51, 2199–204.
Yang, H.-J. &Hakomori, S. (1971) A sphingolipid having a novel type of ceramide and lacto-N-fucopentaose III.J. Biol. Chem. 246, 1192–200.
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Hakomori, SI. Lex and related structures as adhesion molecules. Histochem J 24, 771–776 (1992). https://doi.org/10.1007/BF01046348
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DOI: https://doi.org/10.1007/BF01046348