Skip to main content

Advertisement

SpringerLink
Log in

The roles of Galectin-3 in autoimmunity and tumor progression

  • Immunology in Serbia
  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

Galectin-3, a unique chimera-type member of the β-galactoside-binding soluble lectin family, is widely expressed in numerous cells. Here, we discuss the role of Galectin-3 in T-cell-mediated inflammatory (auto) immunity and tumor rejection by using Galectin-3-deficient mice and four disease models of human pathology: experimental autoimmune encephalomyelitis (EAE), Con-A-induced hepatitis, multiple low-dose streptozotocin-induced diabetes (MLD-STZ diabetes) and metastatic melanoma. We present evidence which suggest that Galectin-3 plays an important pro-inflammatory role in Con-A-induced hepatitis by promoting the activation of T lymphocytes, NKT cells and DCs, cytokine secretion, prevention of M2 macrophage polarization and apoptosis of mononuclear cells, and it leads to severe liver injury. In addition, experiments in Galectin-3-“knock-out” mice indicate that Galectin-3 is also involved in immune-mediated β-cell damage and is required for diabetogenesis in MLD-STZ model by promoting the expression of IFN-gamma, TNF-alpha, IL-17 and iNOS in immune and accessory effector cells. Next, our data demonstrated that Galectin-3 plays an important disease-exacerbating role in EAE through its multifunctional roles in preventing cell apoptosis and increasing IL-17 and IFN-gamma synthesis, but decreasing IL-10 production. Finally, based on our findings, we postulated that expression of Galectin-3 in the host may also facilitate melanoma metastasis by affecting tumor cell adhesion and modulating anti-melanoma immune response, in particular innate antitumor immunity. Taken together, we discuss the evidence of pro-inflammatory and antitumor activities of Galectin-3 and suggest that Galectin-3 may be an important therapeutic target.

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

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Sato S, St-Pierre C, Bhaumik P, Nieminen J. Galectins in innate immunity: dual functions of host soluble beta-galactoside-binding lectins as damage-associated molecular patterns (DAMPs) and as receptors for pathogen-associated molecular patterns (PAMPs). Immunol Rev. 2009;230:172–87.

    Article  PubMed  CAS  Google Scholar 

  2. Henderson NC, Sethi T. The regulation of inflammation by galectin-3. Immunol Rev. 2009;230(1):160–71.

    Article  PubMed  CAS  Google Scholar 

  3. Leffler H, Carlsson S, Hedlund M, Qian Y, Poirier F. Introduction to galectins. Glycoconj J. 2004;19(7–9):433–40.

    PubMed  Google Scholar 

  4. Cooper DN, Barondes SH. God must love galectins; he made so many of them. Glycobiology. 1999;9:979–84.

    Article  PubMed  CAS  Google Scholar 

  5. Yang RY, Rabinovich GA, Liu FT. Galectins: structure, function and therapeutic potential. Expert Rev Mol Med. 2008;10:e17.

    Article  PubMed  Google Scholar 

  6. 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. 2002;23(6):313–20.

    Article  PubMed  CAS  Google Scholar 

  7. Ho MK, Springer TA. Mac-2, a novel 32,000 Mr mouse macrophage subpopulation-specific antigen defined by monoclonal antibodies. J Immunol. 1982;128:1221–8.

    PubMed  CAS  Google Scholar 

  8. 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 bacteria and tissue collagenase. J Biol Chem. 1993;268:26704–11.

    PubMed  CAS  Google Scholar 

  9. Barondes SH, Cooper DN, Gitt MA, Leffler H. Galectins: structure and function of a large family of animal lectins. J Biol Chem. 1994;269(33):20807–10.

    PubMed  CAS  Google Scholar 

  10. Gong HC, Honjo Y, Nangia-Makker P, Hogan V, Mazurak N, Bresalier RS, Raz A. The NH2 terminus of galectin-3 governs cellular compartmentalization and functions in cancer cells. Cancer Res. 1999;59(24):6239–45.

    PubMed  CAS  Google Scholar 

  11. Ochieng J, Green B, Evans S, James O, Warfield P. Modulation of the biological functions of galectin-3 by matrix metalloproteinases. Biochim Biophys Acta. 1998;1379(1):97–106.

    Article  PubMed  CAS  Google Scholar 

  12. Yang RY, Hsu DK, Liu FT. Expression of galectin-3 modulates T-cell growth and apoptosis. Proc Natl Acad Sci USA. 1996;93:6737–42.

    Article  PubMed  CAS  Google Scholar 

  13. Sato S, Hughes RCJ. Regulation of secretion and surface expression of Mac-2, a galactoside-binding protein of macrophages. J Biol Chem. 1994;269:4424–30.

    PubMed  CAS  Google Scholar 

  14. Moutsatsos IK, Wade M, Schindler M, Wang JL. Endogenous lectins from cultured cells: nuclear localization of carbohydrate-binding protein 35 in proliferating 3T3 fibroblasts. Proc Natl Acad Sci USA. 1987;84:6452–6.

    Article  PubMed  CAS  Google Scholar 

  15. Perillo NL, Marcus ME, Baum LG. Galectins: versatile modulators of cell adhesion, cell proliferation, and cell death. J Mol Med. 1998;76:402–12.

    Article  PubMed  CAS  Google Scholar 

  16. Ahmad N, Gabius HJ, André S, Kaltner H, Sabesan S, Roy R, Liu B, Macaluso F, Brewer CF. Galectin-3 precipitates as a pentamer with synthetic multivalent carbohydrates and forms heterogeneous cross-linked complexes. J Biol Chem. 2004;279(12):10841–7.

    Article  PubMed  CAS  Google Scholar 

  17. Liu FT, Rabinovich GA. Galectins as modulators of tumour progression. Nat Rev Cancer. 2005;5:29–41.

    Article  PubMed  CAS  Google Scholar 

  18. Dumic J, Dabelic S, Flögel M. Galectin-3: an open-ended story. Biochim Biophys Acta. 2006;1760:616–35.

    Article  PubMed  CAS  Google Scholar 

  19. Dagher SF, Wang JL, Patterson RJ. Identification of galectin-3 as a factor in pre-mRNA splicing. Proc Natl Acad Sci USA. 1995;92(4):1213–7.

    Article  PubMed  CAS  Google Scholar 

  20. Wang JL, Gray RM, Haudek KC, Patterson RJ. Nucleocytoplasmic lectins. Biochim Biophys Acta. 2004;1673(1–2):75–93.

    Article  PubMed  CAS  Google Scholar 

  21. Califice S, Castronovo V, Bracke M, van den Brûle F. Dual activities of galectin-3 in human prostate cancer: tumor suppression of nuclear galectin-3 vs tumor promotion of cytoplasmic galectin-3. Oncogene. 2004;23(45):7527–36.

    Article  PubMed  CAS  Google Scholar 

  22. Nakahara S, Oka N, Raz A. On the role of galectin-3 in cancer apoptosis. Apoptosis. 2005;10(2):267–75.

    Article  PubMed  CAS  Google Scholar 

  23. Stillman BN, Hsu DK, Pang M, Brewer CF, Johnson P, Liu FT, Baum LG. Galectin-3 and galectin-1 bind distinct cell surface glycoprotein receptors to induce T cell death. J Immunol. 2006;176:778–89.

    PubMed  CAS  Google Scholar 

  24. Fukumori T, Takenaka Y, Yoshii T, Kim HRC, Hogan V, Inohara H, Kagawa S, Raz A. CD29 and CD7 mediate galectin-3-induced type II T-cell apoptosis. Cancer Res. 2003;63:8302–11.

    PubMed  CAS  Google Scholar 

  25. Demetriou M, Granovsky M, Quaggin S, Dennis JW. Negative regulation of T-cell activation and autoimmunity by Mgat5 N-glycosylation. Nature. 2001;409:733–9.

    Article  PubMed  CAS  Google Scholar 

  26. Liu FT, Hsu D K, Zuberi RI, Kuwabara I, Chi EY, Henderson WR Jr. Expression and function of galectin-3, a b-galactoside-binding lectin, in human monocytes and macrophages. Am J Pathol. 1995;147:1016–29.

    Google Scholar 

  27. Sano H, Hsu DK, Yu L, Apgar JR, Kuwabara I, Yamanaka T, Hirashima M, Liu FT. Human galectin-3 is a novel chemoattractant for monocytes and macrophages. J Immunol. 2000;165:2156–64.

    PubMed  CAS  Google Scholar 

  28. Kuwabara I, Liu FT. Galectin-3 promotes adhesion of human neutrophils to laminin. J Immunol. 1996;156:3939–44.

    PubMed  CAS  Google Scholar 

  29. Sato S, Ouellet N, Pelletier I, Simard M, Rancourt A, Bergeron MG. Role of galectin-3 as an adhesion molecule for neutrophil extravasation during streptococcal pneumonia. J Immunol. 2002;168:1813–22.

    PubMed  CAS  Google Scholar 

  30. Christenson K, Matlak M, Björstad Å, Brown KL, Telemo E, Salomonsson E, Leffler H, Bylund J. Galectin-3 functions as an opsonin and enhances the macrophage clearance of apoptotic neutrophils. Glycobiology. 2009;19:16–20.

    PubMed  Google Scholar 

  31. Xiao X, Zhao P, Rodriguez-Pinto D, Qi D, Henegariu O, Alexopoulou L, Flavell A, Wong S, Wen L. Inflammatory regulation by TLR3 in acute hepatitis. J Immunol. 2009;183:3712–9.

    Article  PubMed  CAS  Google Scholar 

  32. Itoh A, Isoda K, Kondoh M, Kawase M, Kobayashi M, Tamesada M, Yagi K. Hepatoprotective effect of syringic acid and vanillic acid on concanavalin a-induced liver injury. Biol Pharm Bull. 2009;32:1215–9.

    Article  PubMed  CAS  Google Scholar 

  33. Wolf AM, Wolf D, Avila MA, Moschen AR, Berasain C, Enrich B, Rumpold H, Tilg H. Up-regulation of the anti-inflammatory adipokine adiponectin in acute liver failure in mice. J Hepatol. 2006;44:537–43.

    Article  PubMed  CAS  Google Scholar 

  34. Hanson JC, Bostick MK, Campe CB, Kodali P, Lee G, Yan J, Maher JJ. Transgenic overexpression of interleukin-8 in mouse liver protects against galactosamine/endotoxin toxicity. J Hepatol. 2006;44:359–67.

    Article  PubMed  CAS  Google Scholar 

  35. Tiegs G, Hentschel J, Wendel A. A T cell-dependent experimental liver injury in mice inducible by concanavalin A. J Clin Invest. 1992;90:196–203.

    Article  PubMed  CAS  Google Scholar 

  36. Gantner F, Leist M, Lohse W, Germann G, Tiegs G. Concanavalin A-induced T-cell-mediated hepatic injury in mice: the role of tumor necrosis factor. Hepatology. 1995;21:190–8.

    PubMed  CAS  Google Scholar 

  37. Volarevic V, Mitrovic M, Milovanovic M, Zelen I, Nikolic I, Mitrovic S, Pejnovic N, Arsenijevic N, Lukic M. Protective role of IL-33/ST2 axis in con A-induced hepatitis. J Hepatol. 2012; 56(1):26–33.

    Article  PubMed  CAS  Google Scholar 

  38. Wang J, Sun R, Wei H, Dong Z, Gao B, Poly TianZ. Poly I: C prevents T cell-mediated hepatitis via an NK-dependent mechanism. J Hepatol. 2006;44:446–54.

    Article  PubMed  CAS  Google Scholar 

  39. Takeda K, Hayakawa Y, Van Kaer L, Matsuda H, Yagita H, Okumura K. Critical contribution of liver natural killer T cells to a murine model of hepatitis. Proc Natl Acad Sci USA. 2000;97:5498–503.

    Article  PubMed  CAS  Google Scholar 

  40. Matsuda Y, Yamagiwa Y, Fukushima K, Ueno Y, Shimosegawa T. Expression of galectin-3 involved in prognosis of patients with hepatocellular carcinoma. Hepatol Res. 2008;38:1098–111.

    Article  PubMed  CAS  Google Scholar 

  41. Wongkham S, Junking M, Wongkham C, Sripa B, Chur-In S, Araki N. Suppression of galectin-3 expression enhances apoptosis and chemosensitivity in liver fluke-associated cholangiocarcinoma. Cancer Sci. 2009;100:2077–84.

    Article  PubMed  CAS  Google Scholar 

  42. Henderson NC, Mackinnon AC, Farnworth SL, Poirier F, Russo FP, Iredale JP, Haslett C, Simpson KJ, Sethi T. Galectin-3 regulates myofibroblast activation and hepatic fibrosis. Proc Natl Acad Sci U S A. 2006;103:5060–5.

    Article  PubMed  CAS  Google Scholar 

  43. Iacobini C, Menini S, Ricci C, Blasetti Fantauzzi C, Scipioni A, Salvi L, Cordone S, Delucchi F, Serino M, Federici M, Pricci F, Pugliese G. Galectin-3 ablation protects mice from diet-induced NASH: a major scavenging role for galectin-3 in liver. J Hepatol. 2011;54(5):975–83.

    Article  PubMed  CAS  Google Scholar 

  44. Joo HG, Goedegebuure PS, Sadanaga N, Nagoshi M, von Bernstorff W, Eberlein TJ. Expression and function of galectin-3, a beta-galactoside-binding protein in activated T lymphocytes. J Leukoc Biol. 2001;69:555–64.

    PubMed  CAS  Google Scholar 

  45. Jeon SB, Yoon HJ, Chang CY, Koh HS, Jeon SH, Park EJ. Galectin-3 exerts cytokine-like regulatory actions through the JAK-STAT pathway. J Immunol. 2010;185:7037–46.

    Article  PubMed  CAS  Google Scholar 

  46. Breuilh L, Vanhoutte F, Fontaine J, van Stijn CM, Tillie-Leblond I, Capron M, Faveeuw C, Jouault T, van Die I, Gosset P, Trottein F. Galectin-3 modulates immune and inflammatory responses during helminthic infection: impact of galectin-3 deficiency on the functions of dendritic cells. Infect Immun. 2007;75:5148–57.

    Article  PubMed  CAS  Google Scholar 

  47. Cumpstey I, Sundin A, Leffler H, Nilsson UJ. C2-symmetrical thiodigalactoside bis-benzamido derivatives as high-affinity inhibitors of galectin-3: efficient lectin inhibition through double arginine-arene interactions. Angew Chem Int Ed Engl. 2005;44(32):5110–12.

    Google Scholar 

  48. Sato S, Nieminen J. Seeing strangers or announcing “danger”: galectin-3 in two models of innate immunity. Glycoconj J. 2004;19(7–9):583–91.

    Google Scholar 

  49. Cerliani JP, Stowell SR, Mascanfroni ID, Arthur CM, Cummings RD, Rabinovich GA. Expanding the universe of cytokines and pattern recognition receptors: galectins and glycans in innate immunity. J Clin Immunol. 2011;31(1):10–21.

    Article  PubMed  CAS  Google Scholar 

  50. van den Berg TK, Honing H, Franke N, van Remoortere A, Schiphorst WE, Liu FT, Deelder AM, Cummings RD, Hokke CH, van Die I. LacdiNAc-glycans constitute a parasite pattern for galectin-3-mediated immune recognition. J Immunol. 2004;173(3):1902–7.

    PubMed  Google Scholar 

  51. John CM, Jarvis GA, Swanson KV, Leffler H, Cooper MD, Huflejt ME, Griffiss JM. Galectin-3 binds lactosaminylated lipooligosaccharides from Neisseria gonorrhoeae and is selectively expressed by mucosal epithelial cells that are infected. Cell Microbiol. 2002;4:649–62.

    Article  PubMed  CAS  Google Scholar 

  52. Pelletier I, Sato S. Specific recognition and cleavage of galectin-3 by Leishmania major through species-specific polygalactose epitope. J Biol Chem. 2002;277(20):17663–70.

    Article  PubMed  CAS  Google Scholar 

  53. Silva-Monteiro E, Reis Lorenzato L, Kenji Nihei O, Junqueira M, Rabinovich GA, Hsu DK, Liu FT, Savino W, Chammas R, Villa-Verde DM. Altered expression of galectin-3 induces cortical thymocyte depletion and premature exit of immature thymocytes during Trypanozoma cruzi infection. Am J Pathol. 2007;170(2):546–56.

    Google Scholar 

  54. Bernardes ES, Silva NM, Ruas LP, Mineo JR, Loyola AM, Hsu DK, Liu FT, Chammas R, Roque-Barreira MC. Toxoplasma gondii infection reveals a novel regulatory role for galectin-3 in the interface of innate and adaptive immunity. Am J Pathol. 2006;168(6):1910–20.

    Article  PubMed  CAS  Google Scholar 

  55. Ruas LP, Bernardes ES, Fermino ML, de Oliveira LL, Hsu DK, Liu FT, Chammas R, Roque-Barreira MC. Lack of galectin-3 drives response to Paracoccidioides brasiliensis toward a Th2-biased immunity. PLoS One. 2009;4(2):e4519.

    Article  PubMed  CAS  Google Scholar 

  56. Jiang HR, Al Rasebi Z, Mensah-Brown E, Shahin A, Xu D, Goodyear CS, Fukada SY, Liu FT, Liew FY, Lukic ML. Galectin-3 deficiency reduces the severity of experimental autoimmune encephalomyelitis. J Immunol. 2009;182(2):1167–73.

    PubMed  CAS  Google Scholar 

  57. Mensah-Brown EP, Shahin A, Al-Shamisi M, Wei X, Lukic ML. IL-23 leads to diabetes induction after subdiabetogenic treatment with multiple low doses of streptozotocin. Eur J Immunol. 2006;36(1):216–23.

    Article  PubMed  CAS  Google Scholar 

  58. Mensah-Brown EP, Al Rabesi Z, Shahin A, Al Shamsi M, Arsenijevic N, Hsu DK, Liu FT, Lukic ML. Targeted disruption of the galectin-3 gene results in decreased susceptibility to multiple low dose streptozotocin-induced diabetes in mice. Clin Immunol. 2009;130:83–8.

    Article  PubMed  CAS  Google Scholar 

  59. Sano H, Hsu DK, Apgar JR, Yu L, Sharma BB, Kuwabara I, Izui S, Liu FT. Critical role of galectin-3 in phagocytosis by macrophages. J Clin Invest. 2003;112(3):389–97.

    PubMed  CAS  Google Scholar 

  60. Cnop M, Welsh N, Jonas JC, Jörns A, Lenzen S, Eizirik DL. Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many differences, few similarities. Diabetes. 2005;54(Suppl 2):S97–107.

    Article  PubMed  CAS  Google Scholar 

  61. Masters SL, Dunne A, Subramanian SL, Hull RL, Tannahill GM, Sharp FA, Becker C, Franchi L, Yoshihara E, Chen Z, Mullooly N, Mielke LA, Harris J, Coll RC, Mills KH, Mok KH, Newsholme P, Nuñez G, Yodoi J, Kahn SE, Lavelle EC, O’Neill LA. Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1beta in type 2 diabetes. Nat Immunol. 2010;11(10):897–04.

    Google Scholar 

  62. Mok SW, Thelen KM, Riemer C, Bamme T, Gültner S, Lütjohann D, Baier M. Simvastatin prolongs survival times in prion infections of the central nervous system. Biochem Biophys Res Commun. 2006;348(2):697–702.

    Article  PubMed  CAS  Google Scholar 

  63. Mok SW, Riemer C, Madela K, Hsu DK, Liu FT, Gültner S, Heise I, Baier M. Role of galectin-3 in prion infections of the CNS. Biochem Biophys Res Commun. 2007;359(3):672–8.

    Article  PubMed  CAS  Google Scholar 

  64. Bellac CL, Coimbra RS, Simon F, Imboden H, Leib SL. Gene and protein expression of galectin-3 and galectin-9 in experimental pneumococcal meningitis. Neurobiol Dis. 2007;28(2):175–83.

    Article  PubMed  CAS  Google Scholar 

  65. Weiner HL. A shift from adaptive to innate immunity: a potential mechanism of disease progression in multiple sclerosis. J Neurol. 2008;255(Suppl 1):3–11.

    Article  PubMed  CAS  Google Scholar 

  66. Liblau RS, Singer SM, McDevitt HO. Th1 and Th2 CD4+ T cells in the pathogenesis of organ-specific autoimmune diseases. Immunol Today. 1995;16(1):34–8.

    Article  PubMed  CAS  Google Scholar 

  67. Steinman L. A rush to judgment on Th17. J Exp Med. 2008;205(7):1517–22.

    Article  PubMed  CAS  Google Scholar 

  68. Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, Wang Y, Hood L, Zhu Z, Tian Q, Dong C. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol. 2005;6(11):1133–41.

    Article  PubMed  CAS  Google Scholar 

  69. Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, McClanahan T, Kastelein RA, Cua DJ. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med. 2005;201(2):233–40.

    Article  PubMed  CAS  Google Scholar 

  70. Grigorian A, Torossian S, Demetriou M. T-cell growth, cell surface organization, and the galectin-glycoprotein lattice. Immunol Rev. 2009;230(1):232–46.

    Article  PubMed  CAS  Google Scholar 

  71. Zhu C, Anderson AC, Schubart A, Xiong H, Imitola J, Khoury SJ, Zheng XX, Strom TB, Kuchroo VK. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol. 2005;6(12):1245–52.

    Article  PubMed  CAS  Google Scholar 

  72. Ohshima S, Kuchen S, Seemayer CA, Kyburz D, Hirt A, Klinzing S, Michel BA, Gay RE, Liu FT, Gay S, Neidhart M. Galectin 3 and its binding protein in rheumatoid arthritis. Arthritis Rheum. 2003;48:2788–95.

    Article  PubMed  CAS  Google Scholar 

  73. Forsman H, Islander U, Andréasson E, Andersson A, Onnheim K, Karlström A, Sävman K, Magnusson M, Brown KL, Karlsson A. Galectin 3 aggravates joint inflammation and destruction in antigen-induced arthritis. Arthritis Rheum. 2011;63:445–54.

    Article  PubMed  CAS  Google Scholar 

  74. Nachtigal M, Al-Assaad Z, Mayer EP, Kim K, Monsigny M. Galectin-3 expression in human atherosclerotic lesions. Am J Pathol. 1988;152:1199–11208.

    Google Scholar 

  75. Iacobini C, Menini S, Ricci C, Scipioni A, Sansoni V, Cordone S, Taurino M, Serino M, Marano G, Federici M, Pricci F, Pugliese G. Accelerated lipid-induced atherogenesis in galectin-3-deficient mice: role of lipoxidation via receptor-mediated mechanisms. Arterioscler Thromb Vasc Biol. 2009;29(6):831–6.

    Article  PubMed  CAS  Google Scholar 

  76. Honjo Y, Nangia-Makker P, Inohara H, Raz A. Downregulation of galectin-3 suppresses tumorigenicity of human breast carcinoma cells. Clin Cancer Res. 2001;7:661–8.

    PubMed  CAS  Google Scholar 

  77. Yoshii T, Inohara H, Takenaka Y, Honjo Y, Akahani S, Nomura T, Raz A, Kubo T. Galectin-3 maintains the transformed phenotype of thyroid papillary carcinoma cells. Int J Oncol. 2001;18(4):787–92.

    PubMed  CAS  Google Scholar 

  78. Elad-Sfadia G, Haklai R, Balan E, Kloog Y. Galectin-3 augments K-Ras activation and triggers a Ras signal that attenuates ERK but not phosphoinositide 3-kinase activity. J Biol Chem. 2004;279(33):34922–30.

    Article  PubMed  CAS  Google Scholar 

  79. Ashery U, Yizhar O, Rotblat B, Elad-Sfadia G, Barkan B, Haklai R, Kloog Y. Spatiotemporal organization of Ras signaling: rasosomes and the galectin switch. Cell Mol Neurobiol. 2006;26(4–6):471–95.

    PubMed  CAS  Google Scholar 

  80. Shimura T, Takenaka Y, Fukumori T, Tsutsumi S, Okada K, Hogan V, Kikuchi A, Kuwano H, Raz A. Implication of galectin-3 in Wnt signaling. Cancer Res. 2005;65(9):3535–7.

    Article  PubMed  CAS  Google Scholar 

  81. Kim HR, Lin HM, Biliran H, Raz A. Cell cycle arrest and inhibition of anoikis by galectin-3 in human breast epithelial cells. Cancer Res. 1999;59:4148–54.

    PubMed  CAS  Google Scholar 

  82. Shimura T, Takenaka Y, Tsutsumi S, Hogan V, Kikuchi A, Raz A. Galectin-3, a novel binding partner of beta-catenin. Cancer Res. 2004;64(18):6363–7.

    Article  PubMed  CAS  Google Scholar 

  83. Inohara H, Raz A. Functional evidence that cell surface galectin-3 mediates homotypic cell adhesion. Cancer Res. 1995;55(15):3267–71.

    PubMed  CAS  Google Scholar 

  84. Inohara H, Akahani S, Koths K, Raz A. Interactions between galectin-3 and Mac-2-binding protein mediate cell–cell adhesion. Cancer Res. 1996;56(19):4530–4.

    PubMed  CAS  Google Scholar 

  85. Khaldoyanidi SK, Glinsky VV, Sikora L, Glinskii AB, Mossine VV, Quinn TP, Glinsky GV, Sriramarao P. MDA-MB-435 human breast carcinoma cell homo- and heterotypic adhesion under flow conditions is mediated in part by Thomsen-Friedenreich antigen-galectin-3 interactions. J Biol Chem. 2003;278:4127–34.

    Article  PubMed  CAS  Google Scholar 

  86. Glinsky VV, Glinsky GV, Rittenhouse-Olson K, Huflejt ME, Glinskii OV, Deutscher SL, Quinn TP. The role of Thomsen-Friedenreich antigen in adhesion of human breast and prostate cancer cells to the endothelium. Cancer Res. 2001;61:4851–7.

    PubMed  CAS  Google Scholar 

  87. Takenaka Y, Fukumori T, Raz A. Galectin-3 and metastasis. Glycoconj J. 2004;19:543–9.

    Article  PubMed  Google Scholar 

  88. Zhao Q, Barclay M, Hilkens J, Guo X, Barrow H, Rhodes JM, Yu LG. Interaction between circulating galectin-3 and cancer-associated MUC1 enhances tumour cell homotypic aggregation and prevents anoikis. Mol Cancer. 2010;9:154.

    Article  PubMed  CAS  Google Scholar 

  89. Méhes G, Witt A, Kubista E, Ambros PF. Circulating breast cancer cells are frequently apoptotic. Am J Pathol. 2001;159:17–20.

    Article  PubMed  Google Scholar 

  90. Kerbel RS, Kobayashi H, Graham CH. Intrinsic or acquired drug resistance and metastasis: are they linked phenotypes? J Cell Biochem. 1994;56(1):37–47.

    Article  PubMed  CAS  Google Scholar 

  91. Matarrese P, Fusco O, Tinari N, Natoli C, Liu FT, Semeraro ML, Malorni W, Iacobelli S. Galectin-3 overexpression protects from apoptosis by improving cell adhesion properties. Int J Cancer. 2000;85(4):545–54.

    Article  PubMed  CAS  Google Scholar 

  92. Matarrese P, Tinari N, Semeraro ML, Natoli C, Iacobelli S, Malorni W. Galectin-3 overexpression protects from cell damage and death by influencing mitochondrial homeostasis. FEBS Lett. 2000;473(3):311–5.

    Article  PubMed  CAS  Google Scholar 

  93. Fukumori T, Kanayama HO, Raz A. The role of galectin-3 in cancer drug resistance. Drug Resist Updat. 2007;10(3):101–8.

    Article  PubMed  CAS  Google Scholar 

  94. O’Driscoll L, Linehan R, Liang YH, Joyce H, Oglesby I, Clynes M. Galectin-3 expression alters adhesion, motility and invasion in a lung cell line (DLKP), in vitro. Anticancer Res. 2002;22(6A):3117–125.

    Google Scholar 

  95. Hood JD, Cheresh DA. Role of integrins in cell invasion and migration. Nat Rev Cancer. 2002;2(2):91–100.

    Article  PubMed  Google Scholar 

  96. Kim SJ, Shin JY, Lee KD, Bae YK, Choi IJ, Park SH, Chun KH. Galectin-3 facilitates cell motility in gastric cancer by up-regulating protease-activated receptor-1 (PAR-1) and matrix metalloproteinase-1 (MMP-1). PLoS One. 2011;6(9):e25103.

    Article  PubMed  CAS  Google Scholar 

  97. 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. 2000;156(3):899–909.

    Article  PubMed  CAS  Google Scholar 

  98. Califice S, Castronovo V, Van Den Brûle F. Galectin-3 and cancer (review). Int J Oncol. 2004;25(4):983–92.

    PubMed  CAS  Google Scholar 

  99. Lurquin C, Lethé B, De Plaen E, Corbière V, Théate I, van Baren N, Coulie PG, Boon T. Contrasting frequencies of antitumor and anti-vaccine T cells in metastases of a melanoma patient vaccinated with a MAGE tumor antigen. J Exp Med. 2005;201(2):249–57.

    Article  PubMed  CAS  Google Scholar 

  100. Carrasco J, Van Pel A, Neyns B, Lethé B, Brasseur F, Renkvist N, van der Bruggen P, van Baren N, Paulus R, Thielemans K, Boon T, Godelaine D. Vaccination of a melanoma patient with mature dendritic cells pulsed with MAGE-3 peptides triggers the activity of nonvaccine anti-tumor cells. J Immunol. 2008;180:3585–93.

    PubMed  CAS  Google Scholar 

  101. Carcelain G, Rouas-Freiss N, Zorn E, Chung-Scott V, Viel S, Faure F, Bosq J, Hercend T. In situ T-cell responses in a primary regressive melanoma and subsequent metastases: a comparative analysis. Int J Cancer. 1997;72(2):241–7.

    Article  PubMed  CAS  Google Scholar 

  102. Gajewski TF, Meng Y, Blank C, Brown I, Kacha A, Kline J, Harlin H. Immune resistance orchestrated by the tumor microenvironment. Immunol Rev. 2006;213:131–45.

    Article  PubMed  CAS  Google Scholar 

  103. Marincola F, Jaffee EM, Hicklin DJ, Ferrone S. Escape of human solid tumors from T-cell recognition: molecular mechanisms and functional significance. Adv Immunol. 2000;74:181–273.

    Article  PubMed  CAS  Google Scholar 

  104. Demotte N, Stroobant V, Courtoy PJ, Van Der Smissen P, Colau D, Luescher IF, Hivroz C, Nicaise J, Squifflet JL, Mourad M, Godelaine D, Boon T, van der Bruggen P. Restoring the association of the T cell receptor with CD8 reverses anergy in human tumor-infiltrating lymphocytes. Immunity. 2008;28(3):414–24.

    Article  PubMed  CAS  Google Scholar 

  105. Zubieta MR, Furman D, Barrio M, Bravo AI, Domenichini E, Mordoh J. Galectin-3 expression correlates with apoptosis of tumor-associated lymphocytes in human melanoma biopsies. Am J Pathol. 2006;168(5):1666–75.

    Article  PubMed  CAS  Google Scholar 

  106. Radosavljevic G, Jovanovic I, Majstorovic I, Mitrovic M, Lisnic VJ, Arsenijevic N, Jonjic S, Lukic ML. Deletion of galectin-3 in the host attenuates metastasis of murine melanoma by modulating tumor adhesion and NK cell activity. Clin Exp Metastasis. 2011;28(5):451–62.

    Article  PubMed  CAS  Google Scholar 

  107. Abdel-Aziz HO, Murai Y, Takasaki I, Tabuchi Y, Zheng HC, Nomoto K, Takahashi H, Tsuneyama K, Kato I, Hsu DK, Liu FT, Hiraga K, Takano Y. Targeted disruption of the galectin-3 gene results in decreased susceptibility to NNK-induced lung tumorigenesis: an oligonucleotide microarray study. J Cancer Res Clin Oncol. 2008;134(7):777–88.

    Google Scholar 

  108. Iurisci I, Tinari N, Natoli C, Angelucci D, Cianchetti E, Iacobelli S. Concentrations of galectin-3 in the sera of normal controls and cancer patients. Clin Cancer Res. 2000;6(4):1389–93.

    PubMed  CAS  Google Scholar 

  109. Vereecken P, Zouaoui Boudjeltia K, Debray C, Awada A, Legssyer I, Sales F, Petein M, Vanhaeverbeek M, Ghanem G, Heenen M. High serum galectin-3 in advanced melanoma: preliminary results. Clin Exp Dermatol. 2006;31(1):105–09.

    Google Scholar 

  110. Dittmar T, Heyder C, Gloria-Maercker E, Hatzmann W, Zänker KS. Adhesion molecules and chemokines: the navigation system for circulating tumor (stem) cells to metastasize in an organ-specific manner. Clin Exp Metastasis. 2008;25(1):11–32.

    Article  PubMed  CAS  Google Scholar 

  111. Krishnan V, Bane SM, Kawle PD, Naresh KN, Kalraiya RD. Altered melanoma cell surface glycosylation mediates organ specific adhesion and metastasis via lectin receptors on the lung vascular endothelium. Clin Exp Metastasis. 2005;22(1):11–24.

    Article  PubMed  CAS  Google Scholar 

  112. Ghiringhelli F, Ménard C, Terme M, Flament C, Taieb J, Chaput N, Puig PE, Novault S, Escudier B, Vivier E, Lecesne A, Robert C, Blay JY, Bernard J, Caillat-Zucman S, Freitas A, Tursz T, Wagner-Ballon O, Capron C, Vainchencker W, Martin F, Zitvogel L. CD4+ CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-beta-dependent manner. J Exp Med. 2005;202(8):1075–85.

    Article  PubMed  CAS  Google Scholar 

  113. Smyth MJ, Teng MW, Swann J, Kyparissoudis K, Godfrey DI, Hayakawa Y. CD4+ CD25+ T regulatory cells suppress NK cell-mediated immunotherapy of cancer. J Immunol. 2006;176(3):1582–7.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study is supported by grants ON175069, ON175071 and ON175103 from Ministry of Education and Science, Republic of Serbia. We thank Milan Milojevic for excellent technical assistance.

Author information

Authors and Affiliations

  1. Center for Molecular Medicine and Stem Cell Research, Faculty of Medicine, University of Kragujevac, Svetozara Markovica 69, 34000, Kragujevac, Serbia

    Gordana Radosavljevic, Vladislav Volarevic, Ivan Jovanovic, Marija Milovanovic, Nada Pejnovic, Nebojsa Arsenijevic & Miodrag L. Lukic

  2. Department of Dermatology, School of Medicine, University of California Davis, Sacramento, CA, USA

    Daniel K. Hsu

Authors
  1. Gordana Radosavljevic
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vladislav Volarevic
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ivan Jovanovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marija Milovanovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nada Pejnovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nebojsa Arsenijevic
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Daniel K. Hsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Miodrag L. Lukic
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Miodrag L. Lukic.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Radosavljevic, G., Volarevic, V., Jovanovic, I. et al. The roles of Galectin-3 in autoimmunity and tumor progression. Immunol Res 52, 100–110 (2012). https://doi.org/10.1007/s12026-012-8286-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12026-012-8286-6

Keywords

Search

Navigation