Glycoconjugate Journal

, Volume 19, Issue 7–9, pp 517–526 | Cite as

Role of galectin-8 as a modulator of cell adhesion and cell growth

  • Yehiel Zick
  • Miriam Eisenstein
  • Rinat A. Goren
  • Yaron R. Hadari
  • Yifat Levy
  • Denise Ronen


Galectin-8 belongs to the family of tandem-repeat type galectins. It consists as several isoforms, each made of two domains of ∼140 amino-acids, both having a carbohydrate recognition domain (CRD). These domains are joined by a ‘link peptide’ of variable length. The human galectin-8 gene covers 33 kbp of genomic DNA. It is localized on chromosome 1 (1q42.11) and contains 11 exons. The gene produces by alternative splicing 14 different transcripts, altogether encoding 6 proteins. Galectin-8, like other galectins, is a secreted protein. Upon secretion galectin-8 acts as a physiological modulator of cell adhesion. When immobilized, it functions as a matrix protein equipotent to fibronectin in promoting cell adhesion by ligation and clustering of a selective subset of cell surface integrin receptors. Complex formation between galectin-8 and integrins involves sugar-protein interactions and triggers integrin-mediated signaling cascades such as Tyr phosphorylation of FAK and paxillin. In contrast, when present in excess as a soluble ligand, galectin-8 (like fibronectin) forms a complex with integrins that negatively regulates cell adhesion. Such a mechanism allows local signals emitted by secreted galectin-8 to specify territories available for cell adhesion and migration. Due to its dual effects on the adhesive properties of cells and its association with fibronectin, galectin-8 might be considered as a novel type of a matricellular protein. Galectin-8 levels of expression positively correlate with certain human neoplasms, prostate cancer being the best example studied thus far. The overexpressed lectin might give these neoplasms some growth and metastasis related advantages due to its ability to modulate cell adhesion and cellular growth. Hence, galectin-8 may modulate cell-matrix interactions and regulate cellular functions in a variety of physiological and pathological conditions. Published in 2004.

galectin-8 cell adhesion cell growth integrins 


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  1. 1.
    Hadari YR, Paz K, Dekel R, Mestrovic T, Accili D, Zick Y, Galectin-8. A new rat lectin, related to galectin-4, J Biol Chem 270, 3447-53 (1995).Google Scholar
  2. 2.
    Hirabayashi J, Satoh M, Kasai K, Evidence that Caenorhabditis elegans 32-kDa beta-galactoside-binding protein is homologous to vertebrate beta-galactoside-binding lectins. cDNA cloning and deduced amino acid sequence, J Biol Chem 267, 15485-90 (1992).Google Scholar
  3. 3.
    Oda Y, Herrmann J, Gitt MA, Turck CW, Burlingame AL, Barondes SH, Leffler H, Soluble lactose-binding lectin from rat intestine with two different carbohydrate-binding domains in the same peptide chain, J Biol Chem 268, 5929-39 (1993).Google Scholar
  4. 4.
    Gitt MA, Colmot C, Xia YR, Atchison RE, Lusis AJ, Poirier F, Barondes S, Leffler H, Galectin-6: A new mammalian Galectin, Glycoconjugate J 12, 548 (1996).Google Scholar
  5. 5.
    Wada J, Kanwar YS, Identification and characterization of galectin-9, a novel beta-galactoside-binding mammalian lectin, J Biol Chem 272, 6078-86 (1997).Google Scholar
  6. 6.
    Yang RY, Hsu DK, Yu L, Ni J, Liu FT, Cell cycle regulation by galectin-12, a new member of the galectin superfamily, J Biol Chem 276, 20252-60 (2001).Google Scholar
  7. 7.
    Wang JL, Laing JG, Anderson RL, Lectins in the cell nucleus, Glycobiology 1, 243-52 (1991).Google Scholar
  8. 8.
    Drickamer K, Taylor ME, Biology of animal lectins, Annu Rev Cell Biol 9, 237-64 (1993).Google Scholar
  9. 9.
    Rini JM, Lobsanov YD, New animal lectin structures, Curr Opin Struct Biol 9, 578-84 (1999).Google Scholar
  10. 10.
    Leffler H, Galectins structure and function—A synopsis, Results Probl Cell Differ 33, 57-83 (2001).Google Scholar
  11. 11.
    Liao F, Shin HS, Rhee SG, Tyrosine phosphorylation of phospholipase C-gamma 1 induced by cross-linking of the high-affinity or low-affinity Fc receptor for IgG in U937 cells, Proc Natl Acad Sci USA 89, 3659-63 (1992).Google Scholar
  12. 12.
    Lobsanov YD, Gitt MA, Leffler H, Barondes SH, Rini JM, X-ray crystal structure of the human dimeric S-Lac lectin, L-14-II, in complex with lactose at 2.9-A resolution, J Biol Chem 268, 27034-38 (1993).Google Scholar
  13. 13.
    Hirabayashi J, Kasai K, Effect of amino acid substitution by sited directed mutagenesis on the carbohydrate recognition and stability of human 14-kDa beta-galactoside-binding lectin, J Biol Chem 266, 23648-53 (1991).Google Scholar
  14. 14.
    Su Z-Z, Lin J, Shen R, Fisher PE, Goldstein NI, Fisher PB, Surface-epitope masking and expression cloning identifies the human prostate carcinoma tumor antigen PCTA-1 a member of the galectin gene family, Proc Natl Acad Sci USA 93, 7252-7 (1996).Google Scholar
  15. 15.
    Bidon N, Brichory F, Hanash S, Bourguet P, Dazord L, Le PJ, Two messenger RNAs and five isoforms for Po66-CBP, a galectin-8 homolog in a human lung carcinoma cell line, Gene 274, 253-62 (2001).Google Scholar
  16. 16.
    Bidon N, Brichory F, Bourguet P, Le PJ, Dazord L, Galectin-8: A complex sub-family of galectins (Review), Int J Mol Med 8, 245-50 (2001).Google Scholar
  17. 17.
    Gopalkrishnan RV, Roberts T, Tuli S, Kang D, Christiansen KA, Fisher PB, Molecular characterization of prostate carcinoma tumor antigen-1,PCTA-1, a human galectin-8 related gene, Oncogene 19, 4405-16 (2000).Google Scholar
  18. 18.
    Hadari YR, Goren R, Levy Y, Amsterdam A, Alon R, Zakut R, Zick Y, Galectin-8 binding to integrins inhibits cell adhesion and induces apoptosis, J Cell Sci 113, 2385-97 (2000).Google Scholar
  19. 19.
    Cooper DN, Massa SM, Barondes SH, Endogenous muscle lectin inhibits myoblast adhesion to laminin, J Cell Biol 115, 1437-48 (1991).Google Scholar
  20. 20.
    Kuwabara I, Liu FT, Galectin-3 promotes adhesion of human neutrophils to laminin, J Immunol 156, 3939-44 (1996).Google Scholar
  21. 21.
    Cleves AE, Cooper DN, Barondes SH, Kelly RB, A new pathway for protein export in Saccharomyces cerevisiae, J Cell Biol 133, 1017-26 (1996).Google Scholar
  22. 22.
    Rubartelli A, Bajetto A, Allavena G, Wollman E, Sitia R, Secretion of thioredoxin by normal and neoplastic cells through a leaderless secretory pathway, J Biol Chem 267, 24161-4 (1992).Google Scholar
  23. 23.
    Siders WM, Klimovitz JC, Mizel SB, Characterization of the structural requirements and cell type specificity of IL-1 alpha and IL-1 beta secretion, J Biol Chem 268, 22170-74 (1993).Google Scholar
  24. 24.
    Mignatti P, Rifkin DB, Release of basic fibroblast growth factor, an angiogenic factor devoid of secretory signal sequence: A trivial phenomenon or a novel secretion mechanism? J Cell Biochem 47, 201-7 (1992).Google Scholar
  25. 25.
    Hadari YR, Eisenstein M, Zakut R, Zick Y, Galectin-8: On the road from structure to function, TIGG 9, 103-12 (1997).Google Scholar
  26. 26.
    Kasai K-I, Hirabayashi J, Galectins: A family of animal lectins that decipher glycocodes, J Biochem 119, 1-8 (1996).Google Scholar
  27. 27.
    Bassen R, Brichory F, Caulet-Maugendre S, Bidon N, Delaval P, Desrues B, Dazord L, Expression of Po66-CBP, a type-8 galectin, in different healthy, tumoral and peritumoral tissues, Anticancer 19, 5429-33 (1999).Google Scholar
  28. 28.
    Hadj SY, Seve AP, Doyennette MM, Saffar L, Felin M, Aubery M, Gattegno L, Hubert J, Nuclear and cytoplasmic expressions of the carbohydrate-binding protein CBP70 in tumoral or healthy cells of the macrophagic lineage, J Cell Biochem 62, 529-42 (1996).Google Scholar
  29. 29.
    Sarafian V, Jadot M, Foidart JM, Letesson JJ, Van-den-Brule F, Castronovo V, Wattiaux R, Coninck SW, Expression of Lamp-1 and Lamp-2 and their interactions with galectin-3 in human tumor cells, Int J Cancer 75, 105-11 (1998).Google Scholar
  30. 30.
    Maldonado CA, Castagna LF, Rabinovich GA, Landa CA, Immunocytochemical study of the distribution of a 16-kDa galectin in the chicken retina, Invest Ophthalmol Vis Sci 40, 2971-17 (1999).Google Scholar
  31. 31.
    Sanford GL, Harris HS, Stimulation of vascular cell proliferation by beta-galactoside specific lectins, FASEB J 4, 2912-8 (1990).Google Scholar
  32. 32.
    Wells V, Mallucci L, Identification of an autocrine negative growth factor: Mouse beta-galactoside binding protein is a cytostatic factor and cell growth regulator, Cell 64, 91-7 (1991).Google Scholar
  33. 33.
    Poirier F, Timmons PM, Chan CT, Guenet JL, Rigby PW, Expression of the L14 lectin during mouse embryogenesis suggests multiple roles during pre-and post-implantation development, Development 115, 143-55 (1992).Google Scholar
  34. 34.
    Retta SF, Ternullo M, Tarone G, Adhesion to matrix proteins, Methods Mol Biol 96, 125-30 (1999).Google Scholar
  35. 35.
    Chiquet-Ehrismann R, Inhibition of cell adhesion by anti-adhesive molecules, Curr Op Cell Biol 7, 715-9 (1995).Google Scholar
  36. 36.
    Geiger B, Bershadsky A, Pankov R, Yamada KM, Transmembrane extracellular matrix-cytoskeleton crosstalk, Nat Rev Mol Cell Biol 2, 793-805 (2001).Google Scholar
  37. 37.
    Sharon N, Lis H, Lectins-proteins with a sweet tooth: Function in cell recognition, Essays in Biochemistry 30, 59-75 (1995).Google Scholar
  38. 38.
    Springer TA, Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration, Annu Rev Physiol 57, 827-72 (1995).Google Scholar
  39. 39.
    Vestweber D, Blanks JE, Mechanisms that regulate the function of the selectins and their ligands, Physiol Rev 79, 181-213 (1999)Google Scholar
  40. 40.
    Kaltner H, Stierstorfer B, Animal lectins as cell adhesion molecules, Acta Anat (Basel) 161, 162-79 (1998).Google Scholar
  41. 41.
    Hughes RC, Galecins as modulators of cell adhesion, Biochimie 83, 667-76 (2001).Google Scholar
  42. 42.
    Rabinovich GA, Baum LG, Tinari N, Paganelli R, Natoli C, Liu FT, Iacobelli S, Galectins and their ligands: Amplifiers, silencers or tuners of the inflammatory response? Trends Immunol 23, 313-20 (2002).Google Scholar
  43. 43.
    Mahanthappa NK, Cooper DNW, Barondes SH, Schwarting GA, Rat olfactory neurins can utilize the endogenous lectin, L-14, in a novel adhesion mechanism, Development 120, 1373-84 (1994).Google Scholar
  44. 44.
    Sato S, Hughes RC, Binding specificity of a baby hamster kidney lectin for H type I and II chains, polylactosamine glycans, and appropriately glycosylated forms of laminin and fibronectin, J Biol Chem 267, 6983-90 (1992).Google Scholar
  45. 45.
    Levy Y, Arbel-Goren R, Hadari YR, Ronen D, Bar-Peled O, Elhanany E, Geiger B, Zick Y, Galectin-8 functions as a matricellular modulator of cell adhesion, J Biol Chem 276, 31285-95 (2001).Google Scholar
  46. 46.
    Schwarzbauer JE, Sechler JL, Fibronectin fibrillogenesis: A paradigm for extracellular matrix assembly, Curr Opin Cell Biol 11, 622-7 (1999).Google Scholar
  47. 47.
    Ochieng J, Leite BM, Warfield P, Regulation of cellular adhesion to extracellular matrix proteins by galectin-3, Biochem Biophys Res Commun 246, 788-91 (1998).Google Scholar
  48. 48.
    Gu M, Wang W, Song WK, Cooper DN, Kaufman SJ, Selective modulation of the interaction of alpha 7 beta 1 integrin with fi-bronectin and laminin by L-14 lectin during skeletal muscle differentiation, J Cell Sci 107, 175-81 (1994).Google Scholar
  49. 49.
    Avni O, Pur Z, Yefenof E, Baniyash M, Complement receptor 3 of macrophages is associated with galectin-1-like protein, J Immunol 160, 6151-8 (1998).Google Scholar
  50. 50.
    Dong S, Hughes RC, Macrophage surface glycoproteins binding to galectin-3 (Mac-2-antigen), Glycoconj J 14, 267-74 (1997).Google Scholar
  51. 51.
    Zamir E, Katz M, Posen Y, Erez N, Yamada KM, Katz BZ, Lin S, Lin DC, Bershadsky A, Kam Z, Geiger B, Dynamics and segregation of cell-matrix adhesions in cultured fibroblasts, Nat Cell Biol 2, 191-6 (2000).Google Scholar
  52. 52.
    Yamada KM, Miyamoto S, Integrin transmembrane signaling and cytoskeletal control, Curr Opin Cell Biol 7, 681-9 (1995).Google Scholar
  53. 53.
    Lyman S, Gilmore A, Burridge K, Gidwitz S, White II GC, Integrin-mediated activation of focal adhesion kinase is independent of focal adhesion formation or integrin activation. Studies with activated and inhibitory beta3 cytoplasmic domain mutants, J Biol Chem 272, 22538-47 (1997).Google Scholar
  54. 54.
    Miyamoto S, Teramoto H, Coso OA, Gutkind JS, Burbelo PD, Akiyama SK, Yamada KM, Integrin function: Molecular hierarchies of cytoskeletal and signaling molecules, J Cell Biol 131, 791-805 (1995).Google Scholar
  55. 55.
    Hynes RO, Cell adhesion: Old and newquestions, Trends Cell Biol 9, M33-7 (1999)Google Scholar
  56. 56.
    Giancotti FG, Ruoslahti E, Integrin signaling, Science 285, 1028-32 (1999).Google Scholar
  57. 57.
    Calof AL, Campanero MR, O'Rear JJ, Yurchenco PD, Lander AD, Domain-specific activation of neuronal migration and neurite outgrowth-promoting activities of laminin, Neuron 13, 117-30 (1994).Google Scholar
  58. 58.
    Yamada KM, Kennedy DW, Dualistic nature of adhesive protein function: Fibronectin and its biologically active peptide fragments can autoinhibit fibronectin function, J Cell Biol 99, 29-36 (1984).Google Scholar
  59. 59.
    Woods ML, Cabanas C, Shimizu Y, Activation-dependent changes in soluble fibronectin binding and expression of beta1 integrin activation epitopes in T cells: Relationship to T cell adhesion and migration, Eur J Immunol 30, 38-49 (2000).Google Scholar
  60. 60.
    Furtak V, Hatcher F, Ochieng J, Galectin-3 mediates the endocytosis of beta-1 integrins by breast carcinoma cells, Biochem Biophys Res Commun 289, 845-50 (2001).Google Scholar
  61. 61.
    Murphy UJ, Lightner VA, Aukhil I, Yan YZ, Erickson HP, Hook M, Focal adhesion integrity is downregulated by the alternatively spliced domain of human tenascin, J Cell Biol 115, 1127-36 (1991).Google Scholar
  62. 62.
    Sage EH, Bornstein P, Extracellular proteins that modulate cell matrix interactions. SPARC, tenascin, thrombospondin, J Biol Chem 266, 14831-4 (1991).Google Scholar
  63. 63.
    Girard JP, Springer TA, Modulation of endothelial cell adhesion by hevin, an acidic protein associated with high endothelial venules, J Biol Chem 271, 4511-7 (1996).Google Scholar
  64. 64.
    Ruoslahti E, Reed CJ, Anchorage dependence, integrins, and apoptosis, Cell 77, 477-8 (1994).Google Scholar
  65. 65.
    Frisch SM, Francis H, Disruption of epithelial cell-matrix interactions induces apoptosis, J Cell Biol 124, 619-26 (1994).Google Scholar
  66. 66.
    Perillo NL, Pace KE, Seilhamer JJ, Baum LG, Apoptosis of T cells mediated by galectin-1, Nature 378, 736-9 (1995).Google Scholar
  67. 67.
    Gorelik E, Galili U, Raz A, On the role of cell surface carbohydrates and their binding proteins (lectins) in tumor metastasis, Cancer Metastasis Rev 20, 245-77 (2001).Google Scholar
  68. 68.
    Camby I, Belot N, Lefranc F, Sadeghi N, de LY, Kaltner H, Musette S, Darro F, Danguy A, Salmon I, Gabius HJ, Kiss R, Galectin-1 modulates human glioblastoma cell migration into the brain through modifications to the actin cytoskeleton and levels of expression of small GTPases, J Neuropathol Exp Neurol 61, 585-96 (2002).Google Scholar
  69. 69.
    Deininger MH, Trautmann K, Meyermann R, Schluesener HJ, Galectin-3 labeling correlates positively in tumor cells and negatively in endothelial cells with malignancy and poor prognosis in oligodendroglioma patients, Anticancer Res 22, 1585-92 (2002).Google Scholar
  70. 70.
    Camby I, Belot N, Rorive S, Lefranc F, Maurage CA, Lahm H, Kaltner H, Hadari Y, Ruchoux MM, Brotchi J, Zick Y, Salmon I, Gabius HJ, Kiss R, Galectins are differentially expressed in supratentorial pilocytic astrocytomas, astrocytomas, anaplastic astrocytomas and glioblastomas, and significantly modulate tumor astrocyte migration, Brain Pathol 11, 12-26 (2001).Google Scholar
  71. 71.
    Wollina U, Graefe T, Feldrappe S, Andre S, Wasano K, Kaltner H, Zick Y, Gabius HJ, Galectin fingerprinting by immuno-and lectin histochemistry in cutaneous lymphoma, J Cancer Res Clin Oncol 128, 103-10 (2002).Google Scholar
  72. 72.
    Simon P, Decaestecker C, Choufani G, Delbrouck C, Danguy A, Salmon I, Zick Y, Kaltner H, Hassid S, Gabius HJ, Kiss R, Darro F. The levels of retinoid RARbeta receptors correlate with galectin-1,-3 and-8 expression in human cholesteatomas, Hear Res 156, 1-9 (2001).Google Scholar
  73. 73.
    Lahm H, Andre S, Hoeflich A, Fischer JR, Sordat B, Kaltner H, Wolf E, Gabius HJ, Comprehensive galectin fingerprinting in a panel of 61 human tumor cell lines by RT-PCR and its implications for diagnostic and therapeutic procedures, J Cancer Res Clin Oncol 127, 375-86 (2001).Google Scholar
  74. 74.
    Nagy N, Bronckart Y, Camby I, Legendre H, Lahm H, Kaltner H, Hadari Y, Van HP, Yeaton P, Pector JC, Zick Y, Salmon I, Danguy A, Kiss R, Gabius HJ, Galectin-8 expression decreases in cancer compared with normal and dysplastic human colon tissue and acts significantly on human colon cancer cell migration as a suppressor, Gut 50, 392-401 (2002).Google Scholar
  75. 75.
    Kayser K, Zink S, Schneider T, Dienemann H, Andre S, Kaltner H, Schuring MP, Zick Y, Gabius HJ, Benign metastasizing leiomyoma of the uterus: Documentation of clinical, immunohistochemical and lectin-histochemical data of ten cases, Virchows Arch 437, 284-92 (2000).Google Scholar
  76. 76.
    Liao DI, Kapadia G, Ahmed H, Vasta GR, Herzberg O, Structure of S-lectin, a developmentally regulated vertebrate beta-galactosidebinding Protein, Proc Natl Acad Sci USA 91, 1428-32 (1994).Google Scholar
  77. 77.
    Levitt M, Molecular dynamics of native protein, I: Computer simulation of trajectories, J Mol Biol 168, 595-620 (1983).Google Scholar
  78. 78.
    Bowie JU, Luthy R, Eisenberg D, A method to identify protein sequences that fold into a known three-dimensional structure, Science 253, 164-70 (1991).Google Scholar
  79. 79.
    Rost B, Sander C, Combining evolutionary information and neural networks to predict protein secondary structure, Proteins 19, 55-72 (1994).Google Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Yehiel Zick
    • 1
  • Miriam Eisenstein
    • 2
  • Rinat A. Goren
    • 1
  • Yaron R. Hadari
    • 1
  • Yifat Levy
    • 1
  • Denise Ronen
    • 1
  1. 1.Department of Molecular Cell BiologyThe Weizmann Institute of ScienceRehovotIsrael
  2. 2.Chemical ServicesThe Weizmann Institute of ScienceRehovotIsrael

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