Skip to main content
SpringerLink
Log in

Carbohydrate-Recognition and Angiogenesis

  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Abstract

Angiogenesis is required for the continual growth of the tumor and provides a gateway for cells to escape the confines of the primary tumor. Angiogenic stimulus triggers a cascade of functional responses leading to local basement membrane dissolution, endothelial cell migration, proliferation and microvessel morphogenesis. In this commentary, we review the significance of carbohydrate-binding proteins involved in angiogenesis. The importance of carbohydrate-recognition processes to angiogenesis stems from the observation that angiogenic factors like fibroblast growth factor family and vascular endothelial growth factors bind initially to the extracellular matrix proteoglycans before binding to their cognate receptors, and some of the adhesion molecules bind to glycoconjugates present on the surface of the endothelial cells. The possible significance of these interactions will be discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Jackson RL, Busch SJ, Cardin AD: Glycosaminoglycans: molecular properties, protein interactions, and role in physiological processes. Physiol Rev 71: 481-539, 1991

    Google Scholar 

  2. Baird A, Klagsbrun M: The fibroblast growth factor family. Cancer Cells 3: 239-243, 1991

    Google Scholar 

  3. Dellian M, Witwer BP, Salehi HA, Yuan F, Jain RK: Quantitation and physiological characterization of angiogenic vessels in mice: effect of basic fibroblast growth factor, vascular endothelial growth factor/vascular permeability factor, and host microenvironment. Am J Pathol 149: 59-71, 1996

    Google Scholar 

  4. Burgess WH, Maciag T: The heparin-binding (fibroblast) growth factor family of proteins. Annu Rev Biochem 58: 575-606, 1989

    Google Scholar 

  5. Gospodarowicz D: Biological activities of fibroblast growth factors. Ann NY Acad Sci 638: 1-8, 1991

    Google Scholar 

  6. Folkman J, Klagsbrun M: Angiogenic factors. Science 235: 442-447, 1987

    Google Scholar 

  7. Wang Y, Becker D: Antisense targeting of basic fibroblast growth factor and fibroblast growth factor receptor-1 in human melanomas blocks intratumoral angiogenesis and tumor growth. Nat Med 3: 887-893, 1997

    Google Scholar 

  8. Konerding MA, Fait F, Dimitropoulou C, Malkusch W, Fern C, Giavazzi R, Coltrini D, Presta M: Impact of fibroblast growth factor-2 on tumor microvascular architecture. A tridimensional morphometric study. Am J Pathol 152: 1607-1616, 1998

    Google Scholar 

  9. Vlodavsky I, Folkman J, Sullivan R, Fridman R. Ishai-Michaeli R, Sasse J, Klagsbrun M: Endothelial cell-derived basic fibroblast growth factor: synthesis and deposition into subendothelial extracellular matrix. Proc Natl Acad Sci USA 84: 2292-2296, 1987

    Google Scholar 

  10. Folkman J, Klagsbrun M, Sasse J, Wadzinski M, Ingber D, Vlodavsky I: A heparin-binding angiogenic protein-basic fibroblast growth factor-is stored within basement membrane. Am J Pathol 130: 393-400, 1988

    Google Scholar 

  11. Pantoliano MW, Horlick RA, Springer BA, Van Dyk DE, Tobery T, Wetmore DR, Lear JD, Nahapetian AT, Bradley JD, Sisk WP: Multivalent ligand-receptor binding interactions in the fibroblast growth factor system produce a cooperative growth factor and heparin mechanism for receptor dimerization. Biochemistry 33: 10229-10248, 1994

    Google Scholar 

  12. Reiland J, Rapraeger AC: Heparan sulfate proteoglycan and FGF receptor target basic FGF to different intracellular destinations. J Cell Sci 105: 1085-1093, 1993

    Google Scholar 

  13. Roghani M, Moscatelli D: Basic fibroblast growth factor is internalized through both receptor-mediated and heparan sulfate-mediated mechanisms. J Biol Chem 267: 22 156-22 162, 1992

    Google Scholar 

  14. Kan M, Wang F, Xu J, Crabb JW, Hou J, McKeehan WL: An essential heparin-binding domain in the fibroblast growth factor receptor kinase. Science 259: 1918-1921, 1993

    Google Scholar 

  15. Ornitz DM, Yayon A, Flanagan JG, Svahn CM, Levi F, Leder P: Heparin is required for cell-free binding of basic fibroblast growth factor to a soluble receptor and for mitogenesis in whole cells. Mol Cell Biol 12: 240-247, 1992

    Google Scholar 

  16. Thompson LD, Pantoliano MW, Springer BA: Energetic characterization of the basic fibroblast growth factor-heparin interaction: identification of the heparin binding domain. Biochemistry 33: 3831-3840, 1994

    Google Scholar 

  17. Li LY, Safran M, Aviezer D, Bohlen P, Seddon AP, Yayon A: Diminished heparin binding of a basic fibroblast growth factor mutant is associated with reduced receptor binding, mitogenesis, plasminogen activator induction, and in vitro angiogenesis. Biochemistry 33: 10999-11007, 1994

    Google Scholar 

  18. Faham S, Hileman RE, Fromm JR, Linhardt RJ, Rees DC: Heparin structure and interactions with basic fibroblast growth factor. Science 271: 1116-1120, 1996

    Google Scholar 

  19. Ornitz DM, Herr AB, Nilsson M, Westman J, Svahn CM, Waksman G: FGF binding and FGF receptor activation by synthetic heparan-derived di-and trisaccharides. Science 268: 432-436, 1995

    Google Scholar 

  20. Moy FJ, Safran M, Seddon AP, Kitchen D, Bohlen P, Aviezer D, Yayon A, Powers R: Properly oriented heparindecasaccharide-induced dimers are the biologically active form of basic fibroblast growth factor. Biochemistry 36: 4782-4791, 1997

    Google Scholar 

  21. Kim KJ, Li B, Winer J, Armanini M, Gillett N, Phillips HS, Ferrara N: Inhibition of vascular endothelial growth factorinduced angiogenesis suppresses tumour growth in vivo. Nature 362: 841-844, 1993

    Google Scholar 

  22. Saleh M, Stacker SA, Wilks AF: Inhibition of growth of C6 glioma cells in vivo by expression of antisense vascular endothelial growth factor sequence. Cancer Res 56: 393-401, 1996

    Google Scholar 

  23. Millauer B, Shawver LK, Plate KH, Risau W, Ullrich A: Glioblastoma growth inhibited in vivo by a dominantnegative Flk-1 mutant. Nature 367: 576-579, 1994

    Google Scholar 

  24. Samoto K, Ikezaki K, Ono M, Shono T, Kohno K, Kuwano M, Fukui M: Expression of vascular endothelial growth factor and its possible relation with neovascularization in human brain tumors. Cancer Res 55: 1189-1193, 1995

    Google Scholar 

  25. Dvorak AM, Kohn S, Morgan ES, Fox P, Nagy JA, Dvorak HF: The vesiculo-vacuolar organelle (VVO): a distinct endothelial cell structure that provides a transcellular pathway for macromolecular extravasation. J Leukoc Biol 59: 100-115, 1996

    Google Scholar 

  26. Esser S, Wolburg K, Wolburg H, Breier G, Kurzchalia T, Risau W: Vascular endothelial growth factor induces endothelial fenestrations in vitro. J Cell Biol 140: 947-959, 1998

    Google Scholar 

  27. Roberts WG, Palade GE: Neovasculature induced by vascular endothelial growth factor is fenestrated. Cancer Res 57: 765-772, 1997

    Google Scholar 

  28. Dvorak HF, Nagy JA, Berse B, Brown LF, Yeo KT, Yeo TK, Dvorak AM, van de Water L, Sioussat TM, Senger DR: Vascular permeability factor, fibrin, and the pathogenesis of tumor stroma formation. Ann NY Acad Sci 667: 101-111, 1992

    Google Scholar 

  29. Shweiki D, Itin A, Soffer D, Keshet E: Vascular endothelial growth factor induced by hypoxia may mediate hypoxiainitiated angiogenesis. Nature 359: 843-845, 1992

    Google Scholar 

  30. Plate KH, Breier G, Weich HA, Risau W: Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature 359: 845-848, 1992

    Google Scholar 

  31. Tischer F, Mitchell R, Hartman T, Silva M, Gospodarowicz D, Fiddes JC, Abraham JA: The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem 266: 11947-11954, 1991

    Google Scholar 

  32. Park JE, Keller GA, Ferrara N: The vascular endothelial growth factor (VEGF) isoforms: differential deposition into the subepithelial extracellular matrix and bioactivity of extracellular matrix-bound VEGF. Mol Biol Cell 4: 1317-1326, 1993

    Google Scholar 

  33. Cohen T, Gitay-Goren H, Sharon R, Shibuya M, Halaban R, Levi BZ, Neufeld G: VFGF121, a vascular endothelial growth factor (VEGF) isoform lacking heparin binding ability, requires cell-surface heparan sulfates for efficient binding to the VFGF receptors of human melanoma cells. J Biol Chem 270: 11322-11326, 1995

    Google Scholar 

  34. Cheng SY, Nagane M, Huang HS, Cavenee WK: Intracerebral tumor-associated hemorrhage caused by overexpression of the vascular endothelial growth factor isoforms VEGF121 and VEGF165 but not VEGF189. Proc Natl Acad Sci USA 94: 12081-12087, 1997

    Google Scholar 

  35. Jonca F, Ortega N, Gleizes PE, Bertrand N, Plouet J: Cell release of bioactive fibroblast growth factor 2 by exon 6-encoded sequence of vascular endothelial growth factor. J Biol Chem 272: 24203-24209, 1997

    Google Scholar 

  36. Gengrinovitch S, Berman B, David G, Witte L, Neufeld G, Ron D: Glypican-1 is a VFGF165 binding proteoglycan that acts as an extracellular chaperone for VFGF165. J Biol Chem 274: 10816-10822, 1999

    Google Scholar 

  37. Schlessinger J, Lax I, Lemmon M: Regulation of growth factor activation by proteoglycans: what is the role of the low affinity receptors? Cell 83: 357-360, 1995

    Google Scholar 

  38. West DC, Kumar S: The effect of hyaluronate and its oligosaccharides on endothelial cell proliferation and monolayer integrity. Exp Cell Res 183: 179-196, 1989

    Google Scholar 

  39. Johnson P, Maiti A, Brown KL, Li R: A role for the cell adhesion molecule CD44 and sulfation in leukocyte-endothelial cell adhesion during an inflammatory response? Biochem Pharmacol 59: 455-465, 2000

    Google Scholar 

  40. Stamenkovic I, Amiot M, Pesando JM, Seed B: A lymphocyte molecule implicated in lymph node homing is a member of the cartilage link protein family. Cell 56: 1057-1062, 1989

    Google Scholar 

  41. Goldstein LA, Zhou DF, Picker LJ, Minty CN, Bargatze RF, Ding JF, Butcher EC: A human lymphocyte homing receptor, the hermes antigen, is related to cartilage proteoglycan core and link proteins. Cell 56: 1063-1072, 1989

    Google Scholar 

  42. Bajorath J, Greenfield B, Munro SB, Day AJ, Aruffo A: Identification of CD44 residues important for hyaluronan binding and delineation of the binding site. J Biol Chem 273: 338-343, 1998

    Google Scholar 

  43. Peach RJ, Hollenbaugh D, Stamenkovic I, Aruffo A: Identi-fication of hyaluronic acid binding sites in the extracellular domain of CD44. J Cell Biol 122: 257-264, 1993

    Google Scholar 

  44. Kohda D, Morton CJ, Parkar AA, Hatanaka H, Inagaki FM, Campbell ID, Day AJ: Solution structure of the link module: a hyaluronan-binding domain involved in extracellular matrix stability and cell migration. Cell 86: 767-775, 1996

    Google Scholar 

  45. Springer TA: Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76: 301-314, 1994

    Google Scholar 

  46. Tedder TF, Steeber DA, Chen A, Engel P: The selectins: vascular adhesion molecules. Faseb J 9: 866-873, 1995

    Google Scholar 

  47. Lasky LA: Selectin-carbohydrate interactions and the initiation of the inflammatory response. Annu Rev Biochem 64: 113-139, 1995

    Google Scholar 

  48. Slevin M, Krupinski J, Kumar S, Gaffney J: Angiogenic oligosaccharides of hyaluronan induce protein tyrosine kinase activity in endothelial cells and activate a cytoplasmic signal transduction pathway resulting in proliferation. Lab Invest 78: 987-1003, 1998

    Google Scholar 

  49. 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

    Google Scholar 

  50. Nguyen M, Strubel NA, Bischoff J: A role for sialyl Lewis-X/A glycoconjugates in capillary morphogenesis. Nature 365: 267-269, 1993

    Google Scholar 

  51. Koch AE, Halloran MM, Haskell CJ, Shah MR, Polverini PJ: Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1. Nature 376: 517-519, 1995

    Google Scholar 

  52. Kraling BM, Razon MJ, Boon LM, Zurakowski D, Seachord C, Darveau RP, Mulliken JB, Corless CL, Bischoff J: E-selectin is present in proliferating endothelial cells in human hemangiomas. Am J Pathol 148: 1181-1191, 1996

    Google Scholar 

  53. Morbidelli L, Brogelli L, Granger HJ, Ziche M: Endothelial cell migration is induced by soluble P-selectin. Life Sci 62: L7-11, 1998

    Google Scholar 

  54. Varki A: Selectin ligands. Proc Natl Acad Sci USA 91: 7390-7397, 1994

    Google Scholar 

  55. Nguyen M, Eilber FR, Defrees S: Novel synthetic analogs of sialyl Lewis X can inhibit angiogenesis in vitro and in vivo. Biochem Biophys Res Commun 228: 716-723, 1996

    Google Scholar 

  56. Gerritsen ME, Shen CP, Atkinson WJ, Padgett RC, Gimbrone Jr. MA, Milstone DS: Microvascular endothelial cells from E-selectin-deficient mice form tubes in vitro. Lab Invest 75: 175-184, 1996

    Google Scholar 

  57. Hartwell DW, Butterfield CE, Frenette PS, Kenyon BM, Hynes RO, Folkman J, Wagner DD: Angiogenesis in P-and E-selectin-deficient mice. Microcirculation 5: 173-178, 1998

    Google Scholar 

  58. Barondes SH, Cooper DN, Gitt MA, Leffler H: Galectins. Structure and function of a large family of animal lectins. J Biol Chem 269: 20 807-20 810, 1994

    Google Scholar 

  59. Herrmann J, Turck CW, Atchison RE, Huflejt ME, Poulter L, Gitt MA, Burlingame AL, Barondes SH, Leffler H: Primary structure of the soluble lactose binding lectin L-29 from rat and dog and interaction of its non-collagenous proline-, glycine-, tyrosine-rich sequence with bacterial and tissue collagenase. J Biol Chem 268: 26 704-26 711, 1993

    Google Scholar 

  60. Akahani S, Nangia-Makker P, Inohara H, Kim HR, Raz A: Galectin-3: a novel antiapoptotic molecule with a functional BHI (NWGR) domain of Bcl-2 family. Cancer Res 57: 5272-5276, 1997

    Google Scholar 

  61. Nangia-Makker P, Akahani S, Bresalier R, Raz A: The role of galectin-3 in metastasis. In: Seve A-P, Caron M (eds) Lectins and Pathology. Harwood Academic Publishers, 2000, pp 67-78

  62. Perillo NL, Marcus ME, Baum LG: Galectins: versatile modulators of cell adhesion, cell proliferation, and cell death. J Mol Med 76: 402-412, 1998

    Google Scholar 

  63. Ochieng J, Green B, Evans S, James O, Warfield P: Modulation of the biological functions of galectin-3 by matrix metalloproteinases. Biochim Biophys Acta 1379: 97-106, 1998

    Google Scholar 

  64. Inohara H, Raz A: Functional evidence that cell surface galectin-3 mediates homotypic cell adhesion. Cancer Res 55: 3267-3271, 1995

    Google Scholar 

  65. Lotan R, Belloni PN, Tressler RJ, Lotan D, Xu XC, Nicolson GL: Expression of galectins on microvessel endothelial cells and their involvement in tumour cell adhesion. Glycoconj J 11: 462-468, 1994

    Google Scholar 

  66. Gordower L, Decaestecker C, Kacem Y, Lemmers A, Gusman J, Burchert M, Danguy A, Gabius H, Salmon I, Kiss R, Camby I: Galectin-3 and galectin-3-binding site expression in human adult astrocytic tumours and related angiogenesis. Neuropathol Appl Neurobiol 25: 319-330, 1999

    Google Scholar 

  67. Nangia-Makker P, Honjo Y, Sarvis R, Akahani S, Hogan V, Pienta KJ, Raz A: Galectin-3 induces endothelial cell morphogenesis and angiogenesis. Am J Pathol 156: 899-909, 2000

    Google Scholar 

  68. Van den Brule F, Castronovo V: Limmin-binding lectins during cancer invation and metastasis. In: Caron M, Seve A-P (eds) Lectins and Pathology. Harwood Academic Publishers, 2000, pp 79-123

  69. Newham P, Humphries MJ: Integrin adhesion receptors: structure, function and implications for biomedicine. Mol Med Today 2: 304-313, 1996

    Google Scholar 

  70. Sheppard D: Epithelial integrins. Bioessays 18: 655-660, 1996

    Google Scholar 

  71. Dejana E, Languino LR, Collella S, Corbascio GC, Plow E, Ginsberg M, Marchisio PC: The localization of a platelet GpIIb-IIIa-related protein in endothelial cell adhension structures. Blood 71: 566-572, 1998

    Google Scholar 

  72. Bischoff J: Cell adhension and angiogenesis. J Clin Invest 99: 373-376, 1997

    Google Scholar 

  73. Stromblad S, Cheresh DA: Integrins, angiogenesis and vascular cell survival. Chem Biol 3: 881-885, 1996

    Google Scholar 

  74. Horton MA: The alpha v beta 3 integrin “vitronectin receptor”. Int J Biochem Cell Biol 29: 721-725, 1997

    Google Scholar 

  75. Ruoslahti E, Pierschbacher MD: Arg-Gly-Asp: a versatile cell recognition signal. Cell 44: 517-518, 1986

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Tumor Progression and Metastasis, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA

    Pratima Nangia-Makker, Sara Baccarini & Avraham Raz

Authors
  1. Pratima Nangia-Makker
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sara Baccarini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Avraham Raz
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nangia-Makker, P., Baccarini, S. & Raz, A. Carbohydrate-Recognition and Angiogenesis. Cancer Metastasis Rev 19, 51–57 (2000). https://doi.org/10.1023/A:1026540129688

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1026540129688

Search

Navigation