Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

The sweet and sour of cancer: glycans as novel therapeutic targets

Nature Reviews Cancer volume 5, pages 526–542 (2005)Cite this article

Key Points

  • Tumours aberrantly express various glycans. Glycans regulate many different aspects of tumour progression, including proliferation, invasion, angiogenesis and metastasis.

  • The proliferation of tumour cells is potentiated by the ability of glycoproteins and glycosphingolipids to directly activate growth-factor receptor tyrosine kinases and by the ability of proteoglycans to function as co-receptors for soluble tumour growth factors.

  • The overexpression of specific glycosyltransferases by tumour cells promotes the formation of tumour glycans that facilitate invasion.

  • Carcinomas commonly overexpress O-linked glycans in the form of cell-surface and secreted mucins that present ligands for adhesion receptors, such as the selectins, which promote the ability of tumour cells to interact with host platelets, leukocytes and endothelial cells. These interactions facilitate haematogenous metastasis of tumour cells.

  • Glycosphingolipids, in the form of gangliosides, are overexpressed by a range of tumours, and their shedding into the bloodstream might impair host immunity to some tumours.

  • During tumour proliferation and invasion, heparan-sulphate proteoglycans (HSPGs) that are present on the surface of tumour cells function as co-receptors to stabilize growth-factor receptor signalling complexes. Secreted HSPGs that are present in the extracellular matrix store growth factors that can be mobilized by the action of tumour heparanases. A similar mechanism that involves endothelial-associated HSPGs and endothelial growth factors facilitates vascular sprouting during tumour angiogenesis.

  • Some glycans can be measured in the bloodstream, and their use as markers of disease burden can be used to screen for specific cancers as well as track response to therapy.

  • Experiments in which glycan function is genetically altered in cell-culture systems or mouse tumour models validate their potential as targets for anticancer therapy.

  • A few glycan-based targeting strategies are currently being tested in clinical trials. As we learn more about the roles of glycans in tumour progression, new targets will continue to emerge for drug design.

Abstract

A growing body of evidence supports crucial roles for glycans at various pathophysiological steps of tumour progression. Glycans regulate tumour proliferation, invasion, haematogenous metastasis and angiogenesis, and increased understanding of these roles sets the stage for developing pharmaceutical agents that target these molecules. Such novel agents might be used alone or in combination with operative and/or chemoradiation strategies for treating cancer.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Important glycans involved in tumour progression.
Figure 2: Stages of tumour progression.
Figure 3: Glycans participate in major pathophysiological events during tumour progression.

References

  1. Wells, L., Vosseller, K. & Hart, G. W. Glycosylation of nucleocytoplasmic proteins: signal transduction and O-GlcNAc. Science 291, 2376–2378 (2001).

    CAS  PubMed  Google Scholar 

  2. Marth, J. Glycosylation changes in ontogeny and cell activation. in Essentials of Glycobiology (eds Varki, A. et al.) 515–536 (Cold Spring Harbor Laboratory Press, New York, 1999).

    Google Scholar 

  3. Varki, A. in Essentials of Glycobiology (eds Varki, A. et al.) 537–549 (Cold Spring Harbor Laboratory Press, New York, 1999).

    Google Scholar 

  4. Feizi, T. Carbohydrate antigens in human cancer. Cancer Surv. 4, 245–269 (1985).

    CAS  PubMed  Google Scholar 

  5. Raedler, A. & Schreiber, S. Analysis of differentiation and transformation of cells by lectins. Crit. Rev. Clin. Lab. Sci. 26, 153–193 (1988).

    CAS  PubMed  Google Scholar 

  6. Weis, W. I. & Drickamer, K. Structural basis of lectin-carbohydrate recognition. Annu. Rev. Biochem. 65, 441–473 (1996). Describes the structural basis for sugar recognition and adhesion by lectins expressed in bacteria, animals and plants.

    CAS  PubMed  Google Scholar 

  7. Bogenrieder, T. & Herlyn, M. Axis of evil: molecular mechanisms of cancer metastasis. Oncogene 22, 6524–6536 (2003).

    CAS  PubMed  Google Scholar 

  8. Hakomori, S. Tumor malignancy defined by aberrant glycosylation and sphingo(glyco)lipid metabolism. Cancer Res. 56, 5309–5318 (1996).

    CAS  PubMed  Google Scholar 

  9. Iozzo, R. V. & San Antonio, J. D. Heparan sulfate proteoglycans: heavy hitters in the angiogenesis arena. J. Clin. Invest. 108, 349–355 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Liu, D., Shriver, Z., Qi, Y., Venkataraman, G. & Sasisekharan, R. Dynamic regulation of tumor growth and metastasis by heparan sulfate glycosaminoglycans. Semin. Thromb. Hemost. 28, 67–78 (2002).

    CAS  PubMed  Google Scholar 

  11. Maeder, T. Sweet medicines. Sci. Am. 287, 40–47 (2002).

    PubMed  Google Scholar 

  12. Hollingsworth, M. A. & Swanson, B. J. Mucins in cancer: protection and control of the cell surface. Nature Rev. Cancer 4, 45–60 (2004).

    CAS  Google Scholar 

  13. Toole, B. P. Hyaluronan: from extracellular glue to pericellular cue. Nature Rev. Cancer 4, 528–539 (2004).

    CAS  Google Scholar 

  14. Felsher, D. W. Reversibility of oncogene-induced cancer. Curr. Opin. Genet. Dev. 14, 37–42 (2004).

    CAS  PubMed  Google Scholar 

  15. Marth, J. in Essentials of Glycobiology (eds Varki, A. et al.) 85–100 (Cold Spring Harbor Laboratory Press, New York, 1999).

    Google Scholar 

  16. Girnita, L. et al. Inhibition of N-linked glycosylation down-regulates insulin-like growth factor-1 receptor at the cell surface and kills Ewing's sarcoma cells: therapeutic implications. Anticancer Drug Des. 15, 67–72 (2000).

    CAS  PubMed  Google Scholar 

  17. Bharathan, S., Moriarty, J., Moody, C. E. & Sherblom, A. P. Effect of tunicamycin on sialomucin and natural killer susceptibility of rat mammary tumor ascites cells. Cancer Res. 50, 5250–5256 (1990).

    CAS  PubMed  Google Scholar 

  18. Komatsu, M., Jepson, S., Arango, M. E., Carothers Carraway, C. A. & Carraway, K. L. Muc4/sialomucin complex, an intramembrane modulator of ErbB2/HER2/Neu, potentiates primary tumor growth and suppresses apoptosis in a xenotransplanted tumor. Oncogene 20, 461–470 (2001). Demonstrates how genetic upregulation of MUC4 in tumour A375 melanoma cells inhibits apoptosis of tumour cells and promotes tumour growth in vivo . MUC4 modulates phosphorylation of the receptor tyrosine kinase in the presence and absence of the major EGF receptor ligand, heregulin.

    CAS  PubMed  Google Scholar 

  19. Hakomori, S. Bifunctional role of glycosphingolipids. Modulators for transmembrane signaling and mediators for cellular interactions. J. Biol. Chem. 265, 18713–18716 (1990).

    CAS  PubMed  Google Scholar 

  20. Nagy, P. et al. Lipid rafts and the local density of ErbB proteins influence the biological role of homo- and heteroassociations of ErbB2. J. Cell Sci. 115, 4251–4262 (2002).

    CAS  PubMed  Google Scholar 

  21. Esko, J. D. in Essentials of Glycobiology (eds Varki, A. et al.) 145–159 (Cold Spring Harbor Laboratory Press, New York, 1999).

    Google Scholar 

  22. Esko, J. D. & Lindahl, U. Molecular diversity of heparan sulfate. J. Clin. Invest. 108, 169–173 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Bernfield, M. et al. Functions of cell surface heparan sulfate proteoglycans. Annu. Rev. Biochem. 68, 729–777 (1999).

    CAS  PubMed  Google Scholar 

  24. Kleeff, J. et al. The cell-surface heparan sulfate proteoglycan glypican-1 regulates growth factor action in pancreatic carcinoma cells and is overexpressed in human pancreatic cancer. J. Clin. Invest. 102, 1662–1673 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Lai, J. et al. Loss of HSulf-1 up-regulates heparin-binding growth factor signaling in cancer. J. Biol. Chem. 278, 23107–23117 (2003). Demonstration of the importance of HSPGs in tumour proliferation. The cell-surface-associated enzyme SULF1 diminishes HSPG sulphation. Downregulation of SULF1 by tumours increases growth-factor signalling and resistance to apoptosis, representing a novel mechanism by which cancer cells can enhance growth.

    CAS  PubMed  Google Scholar 

  26. DeBaun, M. R., Ess, J. & Saunders, S. Simpson Golabi Behmel syndrome: progress toward understanding the molecular basis for overgrowth, malformation, and cancer predisposition. Mol. Genet. Metab. 72, 279–286 (2001).

    CAS  PubMed  Google Scholar 

  27. Filmus, J. Glypicans in growth control and cancer. Glycobiology 11, 19R–23R (2001).

    CAS  PubMed  Google Scholar 

  28. Turley, E. A., Noble, P. W. & Bourguignon, L. Y. Signaling properties of hyaluronan receptors. J. Biol. Chem. 277, 4589–4592 (2002).

    CAS  PubMed  Google Scholar 

  29. Simpson, M. A., Wilson, C. M. & McCarthy, J. B. Inhibition of prostate tumor cell hyaluronan synthesis impairs subcutaneous growth and vascularization in immunocompromised mice. Am. J. Pathol. 161, 849–857 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Misra, S., Ghatak, S., Zoltan-Jones, A. & Toole, B. P. Regulation of multidrug resistance in cancer cells by hyaluronan. J. Biol. Chem. 278, 25285–25288 (2003).

    CAS  PubMed  Google Scholar 

  31. Chou, T. Y. & Hart, G. W. O-linked N-acetylglucosamine and cancer: messages from the glycosylation of c-Myc. Adv. Exp. Med. Biol. 491, 413–418 (2001). Discusses the importance of modification by O -GlcNAc of key cellular oncogenes or tumour-suppressor proteins. O -GlcNAc transferase glycosylates tumour-suppressor proteins at amino-acid residues that either promote oncogene activity or inhibit tumour-suppressor functions, highlighting the importance of O -GlcNAc in tumorigenesis and tumour proliferation.

    CAS  PubMed  Google Scholar 

  32. Noujaim, A. A., Schultes, B. C., Baum, R. P. & Madiyalakan, R. Induction of CA125-specific B and T cell responses in patients injected with MAb-B43.13 — evidence for antibody-mediated antigen-processing and presentation of CA125 in vivo. Cancer Biother. Radiopharm. 16, 187–203 (2001).

    CAS  PubMed  Google Scholar 

  33. Musselli, C. et al. Reevaluation of the cellular immune response in breast cancer patients vaccinated with MUC1. Int. J. Cancer 97, 660–667 (2002).

    CAS  PubMed  Google Scholar 

  34. Ramanathan, R. K. et al. Phase I study of a MUC1 vaccine composed of different doses of MUC1 peptide with SB-AS2 adjuvant in resected and locally advanced pancreatic cancer. Cancer Immunol. Immunother. 54, 254–264 (2005).

    CAS  PubMed  Google Scholar 

  35. Bestagno, M., Occhino, M., Corrias, M. V., Burrone, O. & Pistoia, V. Recombinant antibodies in the immunotherapy of neuroblastoma: perspectives of new developments. Cancer Lett. 197, 193–198 (2003).

    CAS  PubMed  Google Scholar 

  36. Carr, A. et al. Immunotherapy of advanced breast cancer with a heterophilic ganglioside (NeuGcGM3) cancer vaccine. J. Clin. Oncol. 21, 1015–1021 (2003).

    CAS  PubMed  Google Scholar 

  37. Thomas, T. & Thomas, T. J. Polyamine metabolism and cancer. J. Cell Mol. Med. 7, 113–126 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Belting, M. et al. Tumor attenuation by combined heparan sulfate and polyamine depletion. Proc. Natl Acad. Sci. USA 99, 371–376 (2002).

    CAS  PubMed  Google Scholar 

  39. Zeng, C., Toole, B. P., Kinney, S. D., Kuo, J. W. & Stamenkovic, I. Inhibition of tumor growth in vivo by hyaluronan oligomers. Int. J. Cancer 77, 396–401 (1998). Disruption of the interaction between host tissue stromal hyaluronan and the hyaluronan receptor CD44 on tumour cells can be achieved by treatment with hyaluronan oligomers. This study illustrates how infusion with such oligomers can block growth of experimental melanomas in vivo.

    CAS  PubMed  Google Scholar 

  40. Dennis, J. W., Pawling, J., Cheung, P., Partridge, E. & Demetriou, M. UDP-N-acetylglucosamine:α-6-D-mannoside β1, 6 N-acetylglucosaminyltransferase V (Mgat5) deficient mice. Biochim. Biophys. Acta. 1573, 414–422 (2002).

    CAS  PubMed  Google Scholar 

  41. Yoshimura, M., Ihara, Y., Matsuzawa, Y. & Taniguchi, N. Aberrant glycosylation of E-cadherin enhances cell–cell binding to suppress metastasis. J. Biol. Chem. 271, 13811–13815 (1996).

    CAS  PubMed  Google Scholar 

  42. Hirohashi, S. & Kanai, Y. Cell adhesion system and human cancer morphogenesis. Cancer Sci. 94, 575–581 (2003).

    CAS  PubMed  Google Scholar 

  43. Seidenfaden, R., Krauter, A., Schertzinger, F., Gerardy-Schahn, R. & Hildebrandt, H. Polysialic acid directs tumor cell growth by controlling heterophilic neural cell adhesion molecule interactions. Mol. Cell. Biol. 23, 5908–5918 (2003). This study examines the role of polysialic acid on neural cell adhesion molecule (NCAM) in neuroblastoma cells, and demonstrates the ability of polysialic acid to control tumour-cell growth and differentiation by interfering with NCAM signalling at cell–cell contacts.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Angata, K. & Fukuda, M. Polysialyltransferases: major players in polysialic acid synthesis on the neural cell adhesion molecule. Biochimie 85, 195–206 (2003).

    CAS  PubMed  Google Scholar 

  45. Lin, S., Kemmner, W., Grigull, S. & Schlag, P. M. Cell surface α 2, 6 sialylation affects adhesion of breast carcinoma cells. Exp. Cell Res. 276, 101–110 (2002).

    CAS  PubMed  Google Scholar 

  46. Ju, T. & Cummings, R. D. A unique molecular chaperone Cosmc required for activity of the mammalian core 1b 3-galactosyltransferase. Proc. Natl Acad. Sci. USA 99, 16613–16618 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Julien, S. et al. Expression of sialyl-Tn antigen in breast cancer cells transfected with the human CMP-Neu5Ac: GalNAc α2, 6-sialyltransferase (ST6GalNac I) cDNA. Glycoconj. J. 18, 883–893 (2001).

    CAS  PubMed  Google Scholar 

  48. Guo, H. B., Lee, I., Kamar, M., Akiyama, S. K. & Pierce, M. Aberrant N-glycosylation of β1 integrin causes reduced α5β1 integrin clustering and stimulates cell migration. Cancer Res. 62, 6837–6845 (2002).

    CAS  PubMed  Google Scholar 

  49. Wozniak, M. A., Modzelewska, K., Kwong, L. & Keely, P. J. Focal adhesion regulation of cell behavior. Biochim. Biophys. Acta 1692, 103–119 (2004).

    CAS  PubMed  Google Scholar 

  50. Tumova, S., Woods, A. & Couchman, J. R. Heparan sulfate proteoglycans on the cell surface: versatile coordinators of cellular functions. Int. J. Biochem. Cell Biol. 32, 269–288 (2000).

    CAS  PubMed  Google Scholar 

  51. Woods, A., McCarthy, J. B., Furcht, L. T. & Couchman, J. R. A synthetic peptide from the COOH-terminal heparin-binding domain of fibronectin promotes focal adhesion formation. Mol. Biol. Cell 4, 605–613 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Saoncella, S. et al. Syndecan-4 signals cooperatively with integrins in a Rho-dependent manner in the assembly of focal adhesions and actin stress fibers. Proc. Natl Acad. Sci. USA 96, 2805–2810 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Kusano, Y., Yoshitomi, Y., Munesue, S., Okayama, M. & Oguri, K. Cooperation of syndecan-2 and syndecan-4 among cell surface heparan sulfate proteoglycans in the actin cytoskeletal organization of Lewis lung carcinoma cells. J. Biochem. (Tokyo) 135, 129–137 (2004).

    CAS  Google Scholar 

  54. Culp, L. A. et al. Heparan sulfate proteoglycans of Ras-transformed 3T3 or neuroblastoma cells. Differing functions in adhesion on fibronectin. Ann. NY Acad. Sci. 556, 194–216 (1989).

    CAS  PubMed  Google Scholar 

  55. Vlodavsky, I. et al. Inhibition of tumor metastasis by heparanase inhibiting species of heparin. Invasion Metastasis 14, 290–302 (1994).

    CAS  PubMed  Google Scholar 

  56. Vlodavsky, I. & Friedmann, Y. Molecular properties and involvement of heparanase in cancer metastasis and angiogenesis. J. Clin. Invest. 108, 341–347 (2001). Reviews the many roles of heparanase in the tumour environment, and its importance in tumour progression.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Kato, M., Saunders, S., Nguyen, H. & Bernfield, M. Loss of cell surface syndecan-1 causes epithelia to transform into anchorage-independent mesenchyme-like cells. Mol. Biol. Cell 6, 559–576 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Beauvais, D. M. & Rapraeger, A. C. Syndecans in tumor cell adhesion and signaling. Reprod. Biol. Endocrinol. 2, 3 (2004).

    PubMed  PubMed Central  Google Scholar 

  59. Beauvais, D. M., Burbach, B. J. & Rapraeger, A. C. The syndecan-1 ectodomain regulates αvβ3 integrin activity in human mammary carcinoma cells. J. Cell Biol. 167, 171–181 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Sanderson, R. D. Heparan sulfate proteoglycans in invasion and metastasis. Semin. Cell Dev. Biol. 12, 89–98 (2001).

    CAS  PubMed  Google Scholar 

  61. Iida, J., Meijne, A. M., Knutson, J. R., Furcht, L. T. & McCarthy, J. B. Cell surface chondroitin sulfate proteoglycans in tumor cell adhesion, motility and invasion. Semin. Cancer Biol. 7, 155–162 (1996).

    CAS  PubMed  Google Scholar 

  62. Nutt, C. L., Zerillo, C. A., Kelly, G. M. & Hockfield, S. Brain enriched hyaluronan binding (BEHAB)/brevican increases aggressiveness of CNS-1 gliomas in Lewis rats. Cancer Res. 61, 7056–7059 (2001).

    CAS  PubMed  Google Scholar 

  63. Faassen, A. E. et al. A cell surface chondroitin sulfate proteoglycan, immunologically related to CD44, is involved in type I collagen-mediated melanoma cell motility and invasion. J. Cell Biol. 116, 521–531 (1992).

    CAS  PubMed  Google Scholar 

  64. Gunthert, U. et al. A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells. Cell 65, 13–24 (1991).

    CAS  PubMed  Google Scholar 

  65. Aruffo, A., Stamenkovic, I., Melnick, M., Underhill, C. B. & Seed, B. CD44 is the principal cell surface receptor for hyaluronate. Cell 61, 1303–1313 (1990).

    CAS  PubMed  Google Scholar 

  66. Jalkanen, S. & Jalkanen, M. Lymphocyte CD44 binds the COOH-terminal heparin-binding domain of fibronectin. J. Cell Biol. 116, 817–825 (1992).

    CAS  PubMed  Google Scholar 

  67. Wolff, E. A. et al. Generation of artificial proteoglycans containing glycosaminoglycan-modified CD44. Demonstration of the interaction between rantes and chondroitin sulfate. J. Biol. Chem. 274, 2518–2524 (1999).

    CAS  PubMed  Google Scholar 

  68. Vlodavsky, I. et al. Mammalian heparanase: gene cloning, expression and function in tumor progression and metastasis. Nature Med. 5, 793–802 (1999).

    CAS  PubMed  Google Scholar 

  69. Goldshmidt, O. et al. Cell surface expression and secretion of heparanase markedly promote tumor angiogenesis and metastasis. Proc. Natl Acad. Sci. USA 99, 10031–10036 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Vlodavsky, I. et al. Molecular properties and involvement of heparanase in cancer progression and normal development. Biochimie 83, 831–839 (2001).

    CAS  PubMed  Google Scholar 

  71. Jiang, X. & Couchman, J. R. Perlecan and tumor angiogenesis. J. Histochem. Cytochem. 51, 1393–1410 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Adatia, R. et al. Suppression of invasive behavior of melanoma cells by stable expression of anti-sense perlecan cDNA. Ann. Oncol. 8, 1257–1261 (1997).

    CAS  PubMed  Google Scholar 

  73. Zcharia, E. et al. Molecular properties and involvement of heparanase in cancer progression and mammary gland morphogenesis. J. Mammary Gland Biol. Neoplasia 6, 311–322 (2001).

    CAS  PubMed  Google Scholar 

  74. Granovsky, M. et al. Suppression of tumor growth and metastasis in Mgat5-deficient mice. Nature Med. 6, 306–312 (2000). Demonstrates the importance of N -acetylglucosaminyltransferase V (GnTV) in tumour progression by examining mammary tumour growth and metastasis in mice bearing a deletion in the enzyme.

    CAS  PubMed  Google Scholar 

  75. Goss, P. E., Baptiste, J., Fernandes, B., Baker, M. & Dennis, J. W. A phase I study of swainsonine in patients with advanced malignancies. Cancer Res. 54, 1450–1457 (1994).

    CAS  PubMed  Google Scholar 

  76. Schachter, H. The joys of HexNAc. The synthesis and function of N- and O-glycan branches. Glycoconj. J. 17, 465–483 (2000).

    CAS  PubMed  Google Scholar 

  77. Horstkorte, R. et al. Selective inhibition of polysialyltransferase ST8SiaII by unnatural sialic acids. Exp. Cell Res. 298, 268–274 (2004).

    CAS  PubMed  Google Scholar 

  78. Kakkar, A. K. An expanding role for antithrombotic therapy in cancer patients. Cancer Treat. Rev. 29 (Suppl. 2), 23–26 (2003).

    PubMed  Google Scholar 

  79. Bumol, T. F. & Reisfeld, R. A. Unique glycoprotein-proteoglycan complex defined by monoclonal antibody on human melanoma cells. Proc. Natl Acad. Sci. USA 79, 1245–1249 (1982).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Olsen, E. B., Trier, K., Eldov, K. & Ammitzboll, T. Glycosaminoglycans in human breast cancer. Acta Obstet. Gynecol. Scand. 67, 539–542 (1988).

    CAS  PubMed  Google Scholar 

  81. Lee, C. M. et al. Novel chondroitin sulfate-binding cationic liposomes loaded with cisplatin efficiently suppress the local growth and liver metastasis of tumor cells in vivo. Cancer Res. 62, 4282–4288 (2002).

    CAS  PubMed  Google Scholar 

  82. Folkman, J. in The Molecular Basis of Cancer (eds Mendelsohn, J., Howley P. M., Israel M. A. & Liotta L. A.) 206–232 (W. B. Saunders, Philadelphia, 1995).

    Google Scholar 

  83. Marcum, J. A. & Rosenberg, R. D. Heparinlike molecules with anticoagulant activity are synthesized by cultured endothelial cells. Biochem. Biophys. Res. Commun. 126, 365–372 (1985).

    CAS  PubMed  Google Scholar 

  84. Zhou, Z. et al. Impaired angiogenesis, delayed wound healing and retarded tumor growth in perlecan heparan sulfate-deficient mice. Cancer Res. 64, 4699–4702 (2004).

    CAS  PubMed  Google Scholar 

  85. Sharma, B. et al. Antisense targeting of perlecan blocks tumor growth and angiogenesis in vivo. J. Clin. Invest. 102, 1599–1608 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Folkman, J. & Shing, Y. Control of angiogenesis by heparin and other sulfated polysaccharides. Adv. Exp. Med. Biol. 313, 355–364 (1992).

    CAS  PubMed  Google Scholar 

  87. Zcharia, E. et al. Transgenic expression of mammalian heparanase uncovers physiological functions of heparan sulfate in tissue morphogenesis, vascularization, and feeding behavior. FASEB J. 18, 252–263 (2004).

    CAS  PubMed  Google Scholar 

  88. Boehm, T., Folkman, J., Browder, T. & O'Reilly, M. S. Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature 390, 404–407 (1997).

    CAS  PubMed  Google Scholar 

  89. Lapierre, F. et al. Chemical modifications of heparin that diminish its anticoagulant but preserve its heparanase-inhibitory, angiostatic, anti-tumor and anti-metastatic properties. Glycobiology 6, 355–366 (1996).

    CAS  PubMed  Google Scholar 

  90. Parish, C. R., Freeman, C., Brown, K. J., Francis, D. J. & Cowden, W. B. Identification of sulfated oligosaccharide-based inhibitors of tumor growth and metastasis using novel in vitro assays for angiogenesis and heparanase activity. Cancer Res. 59, 3433–3441 (1999).

    CAS  PubMed  Google Scholar 

  91. Presta, M. et al. Heparin derivatives as angiogenesis inhibitors. Curr. Pharm. Des. 9, 553–566 (2003).

    CAS  PubMed  Google Scholar 

  92. Liekens, S. et al. Modulation of fibroblast growth factor-2 receptor binding, signaling, and mitogenic activity by heparin-mimicking polysulfonated compounds. Mol. Pharmacol. 56, 204–213 (1999).

    CAS  PubMed  Google Scholar 

  93. Jemth, P. et al. Biosynthetic oligosaccharide libraries for identification of protein-binding heparan sulfate motifs. Exploring the structural diversity by screening for fibroblast growth factor (FGF)1 and FGF2 binding. J. Biol. Chem. 277, 30567–30573 (2002).

    CAS  PubMed  Google Scholar 

  94. Pisano, C. et al. Undersulfated, low-molecular-weight glycol-split heparin as an antiangiogenic VEGF antagonist. Glycobiology 15, 1C–6C (2005).

    CAS  PubMed  Google Scholar 

  95. Hwang, R. & Varner, J. The role of integrins in tumor angiogenesis. Hematol. Oncol. Clin. North Am. 18, 991–1006, vii (2004).

    PubMed  Google Scholar 

  96. Nguyen, M., Folkman, J. & Bischoff, J. 1-Deoxymannojirimycin inhibits capillary tube formation in vitro. Analysis of N-linked oligosaccharides in bovine capillary endothelial cells. J. Biol. Chem. 267, 26157–26165 (1992).

    CAS  PubMed  Google Scholar 

  97. Krause, T. & Turner, G. A. Are selectins involved in metastasis? Clin. Exp. Metastasis 17, 183–192 (1999).

    CAS  PubMed  Google Scholar 

  98. Borsig, L. et al. Pictures in molecular medicine: three-dimensional visualization of intravascular tumor cells in mice. Trends Mol. Med. 7, 377 (2001).

    CAS  PubMed  Google Scholar 

  99. Cummings, R. D. Selectins. in Essentials of Glycobiology (eds Varki, A. et al.) 391–415 (Cold Spring Harbor Laboratory Press, New York, 1999).

    Google Scholar 

  100. Kim, Y. J., Borsig, L., Varki, N. M. & Varki, A. P-selectin deficiency attenuates tumor growth and metastasis. Proc. Natl Acad. Sci. USA 95, 9325–9330 (1998). Describes the observation that P-selectin is important for the formation of tumour-platelet emboli during metastasis, and facilitates haematogenous dissemination of mucin-producing carcinoma cells.

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Borsig, L., Wong, R., Hynes, R. O., Varki, N. M. & Varki, A. Synergistic effects of L- and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancers of metastasis. Proc. Natl Acad. Sci. USA 99, 2193–2198 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Varki, A. Selectin ligands: will the real ones please stand up? J. Clin. Invest. 100, S31–S35 (1997).

    CAS  PubMed  Google Scholar 

  103. Nakamori, S. et al. Involvement of carbohydrate antigen sialyl Lewis(x) in colorectal cancer metastasis. Dis. Colon Rectum. 40, 420–431 (1997).

    CAS  PubMed  Google Scholar 

  104. Baldus, S. E. et al. Histopathological subtypes and prognosis of gastric cancer are correlated with the expression of mucin-associated sialylated antigens: Sialosyl-Lewis(a), Sialosyl-Lewis(x) and sialosyl-Tn. Tumour Biol. 19, 445–453 (1998).

    CAS  PubMed  Google Scholar 

  105. Nakamori, S. et al. Molecular mechanism involved in increased expression of sialyl Lewis antigens in ductal carcinoma of the pancreas. J. Exp. Clin. Cancer Res. 18, 425–432 (1999).

    CAS  PubMed  Google Scholar 

  106. Muller, A. et al. Involvement of chemokine receptors in breast cancer metastasis. Nature 410, 50–56 (2001).

    CAS  PubMed  Google Scholar 

  107. Almofti, A. et al. The clinicopathological significance of the expression of CXCR4 protein in oral squamous cell carcinoma. Int. J. Oncol. 25, 65–71 (2004).

    CAS  PubMed  Google Scholar 

  108. Crocker, P. R. Siglecs: sialic-acid-binding immunoglobulin-like lectins in cell-cell interactions and signalling. Curr. Opin. Struct. Biol. 12, 609–615 (2002).

    CAS  PubMed  Google Scholar 

  109. Brinkman-Van der Linden, E. C. & Varki, A. New aspects of siglec binding specificities, including the significance of fucosylation and of the sialyl-Tn epitope. Sialic acid-binding immunoglobulin superfamily lectins. J. Biol. Chem. 275, 8625–8632 (2000).

    CAS  PubMed  Google Scholar 

  110. Liu, F. T. & Rabinovich, G. A. Galectins as modulators of tumour progression. Nature Rev. Cancer 5, 29–41 (2005).

    CAS  Google Scholar 

  111. Pearlstein, E., Salk, P. L., Yogeeswaran, G. & Karpatkin, S. Correlation between spontaneous metastatic potential, platelet-aggregating activity of cell surface extracts, and cell surface sialylation in 10 metastatic-variant derivatives of a rat renal sarcoma cell line. Proc. Natl Acad. Sci. USA 77, 4336–4339 (1980).

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Fuster, M. M., Brown, J. R., Wang, L. & Esko, J. D. A disaccharide precursor of sialyl Lewis X inhibits metastatic potential of tumor cells. Cancer Res. 63, 2775–2781 (2003).

    CAS  PubMed  Google Scholar 

  113. Al-Mehdi, A. B. et al. Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells: a new model for metastasis. Nature Med. 6, 100–102 (2000).

    CAS  PubMed  Google Scholar 

  114. Winn, R. K., Liggitt, D., Vedder, N. B., Paulson, J. C. & Harlan, J. M. Anti-P-selectin monoclonal antibody attenuates reperfusion injury to the rabbit ear. J. Clin. Invest. 92, 2042–2047 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Fukuda, M. N. et al. A peptide mimic of E-selectin ligand inhibits sialyl Lewis X-dependent lung colonization of tumor cells. Cancer Res. 60, 450–456 (2000).

    CAS  PubMed  Google Scholar 

  116. Kaila, N. & Thomas, B. E. t. Design and synthesis of sialyl Lewis(x) mimics as E- and P-selectin inhibitors. Med. Res. Rev. 22, 566–601 (2002).

    CAS  PubMed  Google Scholar 

  117. Leppanen, A. et al. A novel glycosulfopeptide binds to P-selectin and inhibits leukocyte adhesion to P-selectin. J. Biol. Chem. 274, 24838–24848 (1999).

    CAS  PubMed  Google Scholar 

  118. Varki, N. M. & Varki, A. Heparin inhibition of selectin-mediated interactions during the haematogenous phase of carcinoma metastasis: rationale for clinical studies in humans. Semin. Thromb. Hemost. 28, 53–66 (2002).

    CAS  PubMed  Google Scholar 

  119. Orner, B. P., Derda, R., Lewis, R. L., Thomson, J. A. & Kiessling, L. L. Arrays for the combinatorial exploration of cell adhesion. J. Am. Chem. Soc. 126, 10808–10809 (2004).

    CAS  PubMed  Google Scholar 

  120. Brown, J. R., Fuster, M. M., Whisenant, T. & Esko, J. D. Expression patterns of α 2, 3-sialyltransferases and α 1, 3-fucosyltransferases determine the mode of sialyl Lewis X inhibition by disaccharide decoys. J. Biol. Chem. 278, 23352–23359 (2003).

    CAS  PubMed  Google Scholar 

  121. Sarkar, A. K., Rostand, K. S., Jain, R. K., Matta, K. L. & Esko, J. D. Fucosylation of disaccharide precursors of sialyl LewisX inhibit selectin-mediated cell adhesion. J. Biol. Chem. 272, 25608–25616 (1997). Demonstrates the ability of disaccharide decoys of glycosylation to alter expression of the glycan selectin ligand SLeX on the surface of lymphoma cells. This is a novel method to reduce the levels of selectin ligands on a range of carcinomas, thereby altering the metastatic potential of tumour cells.

    CAS  PubMed  Google Scholar 

  122. Qian, F., Hanahan, D. & Weissman, I. L. L-selectin can facilitate metastasis to lymph nodes in a transgenic mouse model of carcinogenesis. Proc. Natl Acad. Sci. USA 98, 3976–3981 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Renkonen, J., Paavonen, T. & Renkonen, R. Endothelial and epithelial expression of sialyl Lewis(x) and sialyl Lewis(a) in lesions of breast carcinoma. Int. J. Cancer 74, 296–300 (1997).

    CAS  PubMed  Google Scholar 

  124. Glithero, A. et al. Crystal structures of two H-2Db/glycopeptide complexes suggest a molecular basis for CTL cross-reactivity. Immunity 10, 63–74 (1999).

    CAS  PubMed  Google Scholar 

  125. Ibrahim, N. K. & Murray, J. L. Clinical Development of the STn–KLH Vaccine (Theratope(R)). Clin. Breast Cancer 3 (Suppl. 4), 139–143 (2003). The authors describe the development of a unique tumour vaccine by conjugating a synthetic STn epitope to a high-molecular-weight carrier, KLH. The STn–KLH vaccine generates a humoral and cellular immune response, and its safety was confirmed in the ongoing Phase III trial described in the article.

    Google Scholar 

  126. Holmberg, L. A., Oparin, D. V., Gooley, T. & Sandmaier, B. M. The role of cancer vaccines following autologous stem cell rescue in breast and ovarian cancer patients: experience with the sTn–KLH vaccine (Theratope(R)). Clin. Breast Cancer 3 (Suppl. 4), 144–151 (2003).

    Google Scholar 

  127. de Kleijn, E. M. & Punt, C. J. Biological therapy of colorectal cancer. Eur. J. Cancer 38, 1016–1022 (2002).

    CAS  PubMed  Google Scholar 

  128. Monzavi-Karbassi, B., Cunto-Amesty, G., Luo, P. & Kieber-Emmons, T. Use of surrogate antigens as vaccines against cancer. Hybrid Hybridomics 21, 103–109 (2002).

    CAS  PubMed  Google Scholar 

  129. Lemieux, G. A. & Bertozzi, C. R. Modulating cell surface immunoreactivity by metabolic induction of unnatural carbohydrate antigens. Chem. Biol. 8, 265–275 (2001). Sialic acid is often expressed by tumour-associated oligosaccharide antigens; the authors explored whether intercepting the sialic acid biosynthetic pathway with unnatural precursors might modulate the immunogenicity of targeted tumour cells. Antibodies generated against the unnatural sialic acid directed complement-mediated lysis of tumour cells.

    CAS  PubMed  Google Scholar 

  130. Wolfl, M., Batten, W. Y., Posovszky, C., Bernhard, H. & Berthold, F. Gangliosides inhibit the development from monocytes to dendritic cells. Clin. Exp. Immunol. 130, 441–448 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Caldwell, S. et al. Mechanisms of ganglioside inhibition of APC function. J. Immunol. 171, 1676–1683 (2003).

    CAS  PubMed  Google Scholar 

  132. Freeze, H. H., Sampath, D. & Varki, A. α- and β-xylosides alter glycolipid synthesis in human melanoma and Chinese hamster ovary cells. J. Biol. Chem. 268, 1618–1627 (1993).

    CAS  PubMed  Google Scholar 

  133. Weiss, M., Hettmer, S., Smith, P. & Ladisch, S. Inhibition of melanoma tumor growth by a novel inhibitor of glucosylceramide synthase. Cancer Res. 63, 3654–3658 (2003).

    CAS  PubMed  Google Scholar 

  134. Ragupathi, G. et al. Consistent antibody response against ganglioside GD2 induced in patients with melanoma by a GD2 lactone-keyhole limpet hemocyanin conjugate vaccine plus immunological adjuvant QS-21. Clin. Cancer Res. 9, 5214–5220 (2003).

    CAS  PubMed  Google Scholar 

  135. Slovin, S. F. et al. Carbohydrate vaccines in cancer: immunogenicity of a fully synthetic globo H hexasaccharide conjugate in man. Proc. Natl Acad. Sci. USA 96, 5710–5715 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  136. Pagnan, G. et al. Delivery of c-myb antisense oligodeoxynucleotides to human neuroblastoma cells via disialoganglioside GD(2)-targeted immunoliposomes: antitumor effects. J. Natl Cancer Inst. 92, 253–261 (2000).

    CAS  PubMed  Google Scholar 

  137. Nakagoe, T. et al. Difference in prognostic value between sialyl Lewis(a) and sialyl Lewis(x) antigen levels in the preoperative serum of gastric cancer patients. J. Clin. Gastroenterol. 34, 408–415 (2002).

    CAS  PubMed  Google Scholar 

  138. Nakagoe, T. et al. Preoperative serum level of CA19–9 predicts recurrence after curative surgery in node-negative colorectal cancer patients. Hepatogastroenterology 50, 696–699 (2003).

    PubMed  Google Scholar 

  139. Satoh, H. et al. Predictive value of preoperative serum sialyl Lewis X-i antigen levels in non-small cell lung cancer. Anticancer Res. 18, 2865–2868 (1998).

    CAS  PubMed  Google Scholar 

  140. Seelenmeyer, C., Wegehingel, S., Lechner, J. & Nickel, W. The cancer antigen CA125 represents a novel counter receptor for galectin-1. J. Cell Sci. 116, 1305–1318 (2003).

    CAS  PubMed  Google Scholar 

  141. Hayashi, N. et al. Association between expression levels of CA 19–9 and N-acetylglucosamine-β;1, 3-galactosyltransferase 5 gene in human pancreatic cancer tissue. Pathobiology 71, 26–34 (2004).

    PubMed  Google Scholar 

  142. Schroeder, J. A., Adriance, M. C., Thompson, M. C., Camenisch, T. D. & Gendler, S. J. MUC1 alters β-catenin-dependent tumor formation and promotes cellular invasion. Oncogene 22, 1324–1332 (2003).

    CAS  PubMed  Google Scholar 

  143. Luchansky, S. J., Goon, S. & Bertozzi, C. R. Expanding the diversity of unnatural cell-surface sialic acids. Chembiochem. 5, 371–374 (2004).

    CAS  PubMed  Google Scholar 

  144. Saxon, E. & Bertozzi, C. R. Cell surface engineering by a modified Staudinger reaction. Science 287, 2007–2010 (2000).

    CAS  PubMed  Google Scholar 

  145. Dwek, R. A., Butters, T. D., Platt, F. M. & Zitzmann, N. Targeting glycosylation as a therapeutic approach. Nature Rev. Drug Discov. 1, 65–75 (2002).

    CAS  Google Scholar 

  146. Brown, J. R., Fuster, M. M. & Esko, J. D. in Carbohydrate Based Drug Discovery, Vol. 2 (ed. Wong, C.-H.) 883–898 (Wiley VCH, Weinheim, 2003).

    Google Scholar 

  147. Fritz, T. A., Lugemwa, F. N., Sarkar, A. K. & Esko, J. D. Biosynthesis of heparan sulfate on β-D-xylosides depends on aglycone structure. J. Biol. Chem. 269, 300–307 (1994).

    CAS  PubMed  Google Scholar 

  148. Dimitroff, C. J., Sharma, A. & Bernacki, R. J. Cancer metastasis: a search for therapeutic inhibition. Cancer Invest. 16, 279–290 (1998).

    CAS  PubMed  Google Scholar 

  149. Prescher, J. A., Dube, D. H. & Bertozzi, C. R. Chemical remodelling of cell surfaces in living animals. Nature 430, 873–877 (2004).

    CAS  PubMed  Google Scholar 

  150. Takenaka, Y., Fukumori, T. & Raz, A. Galectin-3 and metastasis. Glycoconj. J. 19, 543–549 (2004).

    Google Scholar 

  151. Kojima, N. & Hakomori, S. Cell adhesion, spreading, and motility of GM3-expressing cells based on glycolipid-glycolipid interaction. J. Biol. Chem. 266, 17552–17558 (1991).

    CAS  PubMed  Google Scholar 

  152. Pili, R. et al. The α-glucosidase I inhibitor castanospermine alters endothelial cell glycosylation, prevents angiogenesis, and inhibits tumor growth. Cancer Res. 55, 2920–2926 (1995).

    CAS  PubMed  Google Scholar 

  153. Kleeff, J. et al. Stable transfection of a glypican-1 antisense construct decreases tumorigenicity in PANC-1 pancreatic carcinoma cells. Pancreas 19, 281–288 (1999).

    CAS  PubMed  Google Scholar 

  154. Miyamoto, S. et al. Heparin-binding EGF-like growth factor is a promising target for ovarian cancer therapy. Cancer Res. 64, 5720–5727 (2004).

    CAS  PubMed  Google Scholar 

  155. Derksen, P. W. et al. Cell surface proteoglycan syndecan-1 mediates hepatocyte growth factor binding and promotes Met signaling in multiple myeloma. Blood 99, 1405–1410 (2002).

    CAS  PubMed  Google Scholar 

  156. Mercurio, A. M., Bachelder, R. E., Bates, R. C. & Chung, J. Autocrine signaling in carcinoma: VEGF and the α6β4 integrin. Semin. Cancer Biol. 14, 115–122 (2004).

    CAS  PubMed  Google Scholar 

  157. Syrokou, A., Tzanakakis, G. N., Hjerpe, A. & Karamanos, N. K. Proteoglycans in human malignant mesothelioma. Stimulation of their synthesis induced by epidermal, insulin and platelet-derived growth factors involves receptors with tyrosine kinase activity. Biochimie 81, 733–744 (1999).

    CAS  PubMed  Google Scholar 

  158. George, D. Targeting PDGF receptors in cancer—rationales and proof of concept clinical trials. Adv. Exp. Med. Biol. 532, 141–151 (2003).

    CAS  PubMed  Google Scholar 

  159. Wang, L., Fuster, M. M., Sriranardo, P. & Esko, J. D. Endothelial deficiency of heparan sulphate impairs L-selectin and chemokine mediated neutrophil trafficking during inflammatory responses. Nature Immunol. (in the press).

Download references

Acknowledgements

We would like to thank A. Varki for many helpful comments. This work was supported by a Research Career Development Award from the US Department of Veteran's Affairs (to M.F.) and National Institutes of Health (to J.D.E.).

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California, San Diego, La Jolla, 92093-0687, California, USA

    Mark M. Fuster

  2. Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, 92093-0687, California, USA

    Jeffrey D. Esko

Authors
  1. Mark M. Fuster
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jeffrey D. Esko
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeffrey D. Esko.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

DATABASES

Entrez Gene

CD44

COSMC

E-cadherin

EGF

ERBB2

FGF2

glypican-1

glypican-3

HB-EGF

IGF1R

IL-8

MUC1

MUC16

MUC4

TGFβ

VEGF

National Cancer Institute

breast cancer

melanoma

ovarian cancer

pancreatic cancer

FURTHER INFORMATION

Complex Carbohydrate Research Center

Consortium for Functional Glycomics

Glycobiology journal

Glycobiology Research and Training Center

National Cancer Institute Glycobiology Resources

Oxford Glycobiology Institute

Society for Glycobiology

Glossary

GLYCOCONJUGATE

A molecule in which one or more glycan units are covalently linked to a non-carbohydrate entity.

N-LINKED GLYCANS

Glycans covalently linked to an asparagine residue of a polypeptide chain in the consensus sequence–Asn–X–Ser/Thr.

GLYCOPROTEIN

A protein with one or more covalently bound glycans.

O-LINKED GLYCANS

Glycans glycosidically linked to the hydroxyl group of the amino acids serine, threonine, tyrosine or hydroxylysine.

MUCINS

Large glycoproteins with a high content of serine, threonine and proline residues, and numerous O-linked glycans, often occurring in clusters on the polypeptide. Tumour mucins are often decorated by unique small glycans such as Tn (O-linked GalNAc) or sialyl Tn antigens (sialic acid-capped O-linked GalNAc).

PROTEOGLYCAN

A protein with one or more covalently attached glycosaminoglycan chains, such as heparan sulphate or chondroitin sulphate (and dermatan sulphate). In the tumour environment, a range of heparan-sulphate proteoglycans expressed by both tumour cells as well as endothelial cells affect growth-factor signalling.

GLYCOCALYX

The cell-coat structure consisting of glycans and glycoconjugates surrounding animal cells. This is seen as an electron-dense layer by electron microscopy.

LECTIN

A protein (other than an anti-carbohydrate antibody) that specifically recognizes and binds to glycans without catalysing a modification of the glycan.

EGF-RECEPTOR FAMILY

Epidermal growth factor receptors have important roles in initiating the signalling that directs the behaviour of epithelial cells and tumours of epithelial origin. The four members of the family are also known as ERBB receptor tyrosine kinases (ERBB1–4), and share structural and functional similarities.

GANGLIOSIDES

Anionic glycosphingolipids containing one or more residues of sialic acid.

LIPID RAFTS

Microdomains in the plasma membrane that are enriched in sphingolipids, cholesterol and GPI-linked proteins. They function as signalling platforms through their ability to concentrate signalling proteins, resulting in increased output from receptors that require cross-activating interactions and increasing local concentrations of other downstream signalling components.

SELECTINS

C-type calcium-dependent lectin expressed by cells in the vasculature and bloodstream. The three known selectins are L-selectin/CD62L (expressed by most leukocytes), E-selectin/CD62E (expressed by cytokine-activated endothelial cells) and P-selectin/CD62P (expressed by activated endothelial cells and platelets). Important ligands for the selectins include glycans containing sialyl Lewis X and sialyl Lewis A.

METASTATIC SEEDING

The colonization of an organ or tissue by metastatic tumour cells.

LEWIS TYPE BLOOD GROUP ANTIGENS

A structurally similar set of fucose-containing (α1-3-fucosylated) oligosaccharides found on normal epithelia and blood cells, a few of which (for example, the sialyl Lewis X or sialyl Lewis Y antigens) are overexpressed on the surface of certain epithelial tumour cells.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Fuster, M., Esko, J. The sweet and sour of cancer: glycans as novel therapeutic targets. Nat Rev Cancer 5, 526–542 (2005). https://doi.org/10.1038/nrc1649

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrc1649

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing