Medical Oncology

, Volume 28, Supplement 1, pp 675–684 | Cite as

Biochemical, pathological and oncological relevance of Gb3Cer receptor

  • D. ĐevenicaEmail author
  • V. Čikeš Čulić
  • A. Vuica
  • A. Markotić
Original paper


Glycosphingolipids are amphipathic molecules composed of hydrophilic oligosaccharide chain and a hydrophobic ceramide part, located primarily in the membrane microdomains of animal cells. Their oligosaccharide chains make them excellent candidates for the cell surface recognition molecules. Natural glycosphingolipid, globotriaosylceramide (Gal α1-4, Gal β1-4, Glc β1-1, ceramide), is also called CD77 and its expression was previously associated with proliferating centroblasts undergoing somatic hypermutation, but it has been demonstrate that globotriaosylceramide is not a reliable marker to discriminate human centroblasts from centrocytes. Globotriaosylceramide constitutes rare P k blood group antigen on erythrocytes, and it is also known as Burkitt’s lymphoma antigen. On endothelial cells, globotriaosylceramide plays as the receptor for bacterial toxins of the Shiga family, also called verotoxins. Precise biological function and significance of globotriaosylceramide expression on endothelial cells remains to be the subject of many studies and it is believed globotriaosylceramide represents an example of a glycolipid antigen able to transduce a signal leading to apoptosis. In past decade, cancer researches put a great afford in determining new therapeutic agents such as bacterial toxins against tumor malignancies. Reports have demonstrated that verotoxin-1 induces apoptosis in solid tumor cell lines expressing globotriaosylceramide such as astrocytoma, renal cell carcinoma, colon cancer and breast cancer due to verotoxin-1 high specificity and apoptosis-inducing properties, and therefore, it is suggested to be an anticancer agent. Verotoxins have been investigated weather they could reduce treatment side-effects and toxicity to normal tissues and become a new oncological tool in cancer labeling.


Glycosphingolipids Verotoxins Lipid rafts Endothelial apoptosis Antibody-based cancer immunotherapy 



This work resulted from scientific project “Pathobiochemistry of glycosphingolipid antigens” carried out by support of Ministry of Science, Education and Sports, Republic of Croatia.


  1. 1.
    Hakomori SI. Cell adhesion/recognition and signal transduction through glycosphingolipid microdomain. Glycoconj J. 2000;17:143–51.PubMedGoogle Scholar
  2. 2.
    Sonnino S, Prinetti A, Mauri L, Chigorno V, Tettamanti G. Dynamic and structural properties of sphingolipids as driving forces for the formation of membrane domains. Chem Rev. 2006;106:2111–25.PubMedGoogle Scholar
  3. 3.
    Fantini J, Maresca M, Hammache D, Yahi N, Delézay O. Glycosphingolipid (GSL) microdomains as attachment platforms for host pathogens and their toxins on intestinal epithelial cells: activation of signal transduction pathways and perturbations of intestinal absorption and secretion. Glycoconj J. 2001;17:173–9.Google Scholar
  4. 4.
    Stults CL, Sweeley CC, Macher BA. Glycosphingolipids: structure, biological source, and properties. Method Enzymol. 1989;179:167–214.Google Scholar
  5. 5.
    Schnaar RL. Glycosphingolipids in cell surface recognition. Glycobiology. 1991;1:477–85.PubMedGoogle Scholar
  6. 6.
    Lingwood CA. Role of verotoxin receptors in pathogenesis. Trends Microbiol. 1996;4:147–53.PubMedGoogle Scholar
  7. 7.
    Konowalchuk J, Dickie N, Stavric S, Speirs JI. Properties of an Escherichia coli cytotoxin. Infect Immun. 1978;20:575–7.PubMedGoogle Scholar
  8. 8.
    Sandvig K. Shiga toxins. Toxicon. 2001;39:1629–35.PubMedGoogle Scholar
  9. 9.
    Boyd B, et al. Lipid modulation of glycolipid receptor function. Eur J Biochem. 1994;223:873–8.PubMedGoogle Scholar
  10. 10.
    Kiarash A, et al. Glycosphingolipid receptor function is modified by fatty acid content. J Biol Chem. 1994;269:11138–46.PubMedGoogle Scholar
  11. 11.
    Lingwood CA. Aglycone modulation of glycolipid receptor function. Glycoconj J. 1996;13:495–503.PubMedGoogle Scholar
  12. 12.
    Arab S, Lingwood CA. Intracellular targeting of the endoplasmic reticulum/nuclear envelope by retrograde transport may determine cell hypersensitivity to verotoxin via globotriaosyl ceramide fatty isoform traffic. J Cell Physiol. 1998;177:646–60.PubMedGoogle Scholar
  13. 13.
    Ling H, et al. Structure of the shiga-like toxin I B-pentamer complexed with an analogue of its receptor Gb3. Biochemistry. 1998;37:1777–88.PubMedGoogle Scholar
  14. 14.
    Sandvig K, van Deurs B. Entry of ricin and Shiga toxin into cells: molecular mechanisms and medical perspectives. EMBO J. 2000;19:5943–50.PubMedGoogle Scholar
  15. 15.
    Garred O, van Deurs B, Sandvig K. Furin-induced cleavage and activation of Shiga toxin. J Biol Chem. 1995;270:10817–21.PubMedGoogle Scholar
  16. 16.
    Endo Y, et al. Site of action of a Vero toxin (VT2) from Escherichia coli O157:H7 and Shiga toxin on eukaryotic ribosomes. Eur J Biochem. 1988;171:45–50.PubMedGoogle Scholar
  17. 17.
    Mangeney M, et al. Apoptosis induced in Burkitt’s lymphoma cells via Gb3/CD77, a glycolipid antigen. Cancer Res. 1993;53:5314–9.PubMedGoogle Scholar
  18. 18.
    Fan J, Sammalkorpi M, Haataja M. Formation and regulation of lipid microdomains in cell membranes: theory, modeling, and speculation. FEBS Lett. 2010;584:1678–84.PubMedGoogle Scholar
  19. 19.
    Gaus K, Chklovskaia E, Fazekas de Groth B, Jessup W, Harder T. Condensation of the plasma membrane at the site of T lymphocyte activation. J Cell Biol. 2005;171:121–31.PubMedGoogle Scholar
  20. 20.
    Tavano R, et al. CD28 interaction with filamin-A controls lipid raft accumulation at the T-cell immunological synapse. Nat Cell Biol. 2006;8:1270–6.PubMedGoogle Scholar
  21. 21.
    Chinnapen DJ, Chinnapen H, Saslowsky D, Lencer WI. Rafting with cholera toxin: endocytosis and trafficking from plasma membrane to ER. FEMS Microbiol Lett. 2007;266:129–37.PubMedGoogle Scholar
  22. 22.
    Kalisiak A, Minniti JG, Oosterwijk E, Old LJ, Scheinberg DA. Neutral glycosphingolipid expression in B-cell neoplasms. Int J Cancer. 1991;49:837–45.PubMedGoogle Scholar
  23. 23.
    Sandvig K, et al. Pathways followed by ricin and Shiga toxin into cells. Histochem Cell Biol. 2002;117:131–41.PubMedGoogle Scholar
  24. 24.
    Bonifacino JS, Rojas R. Retrograde transport from endosomes to the trans-Golgi network. Nat Rev Mol Cell Biol. 2006;7:568–79.PubMedGoogle Scholar
  25. 25.
    Römer W, et al. Shiga toxin induces tubular membrane invaginations for its uptake into cells. Nature. 2007;450:670–5.PubMedGoogle Scholar
  26. 26.
    Mori T, et al. Globotriaosyl ceramide (CD77/Gb3) in the glycolipidenriched membrane domain participates in B-cell receptor-mediated apoptosis by regulating Lyn kinase activity in human B cells. Exp Hematol. 2000;28:1260–8.PubMedGoogle Scholar
  27. 27.
    Katagiri YU, et al. Activation of Src family kinase yes induced by Shiga toxin binding to globotriaosyl ceramide (Gb3/CD77) in low density, detergent-insoluble microdomains. J Biol Chem. 1999;274:35278–82.PubMedGoogle Scholar
  28. 28.
    Falguières T, et al. Targeting of Shiga toxin B-subunit to retrograde transport route in association with detergent resistant membranes. Mol Biol Cell. 2001;12:2453–68.PubMedGoogle Scholar
  29. 29.
    Kovbasnjuk O, et al. Role of lipid rafts in Shiga toxin 1 interaction with the apical surface of Caco-2 cells. J Cell Sci. 2001;114:4025–31.PubMedGoogle Scholar
  30. 30.
    Lencer WI, Saslowsky D. Raft trafficking of AB5 subunit bacterial toxins. Biochim Biophys Acta. 2005;1746:314–21.PubMedGoogle Scholar
  31. 31.
    Tam P, Lingwood C. Membrane-cytosolic translocation of verotoxin A1-subunit in target cells. Microbiology. 2007;153:2700–10.PubMedGoogle Scholar
  32. 32.
    Römer W, et al. Actin dynamics drive membrane reorganization and scission in clathrin-independent endocytosis. Cell. 2010;140:540–53.PubMedGoogle Scholar
  33. 33.
    Binnington B, Lingwood D, Nutikka A, Lingwood CA. Effect of globotriaosyl ceramide fatty acid a-hydroxylation on the binding by verotoxin 1 and verotoxin 2. Neurochem Res. 2002;27:807–13.PubMedGoogle Scholar
  34. 34.
    Newburg D, et al. Susceptibility to hemolytic-uremic syndrome relates to erythrocyte glycosphingolipid patterns. J Infect Dis. 1993;168:476–9.PubMedGoogle Scholar
  35. 35.
    Lingwood CA. Verotoxin/globotriaosyl ceramide recognition: angiopathy, angiogenesis and antineoplasia. Biosci Rep. 1999;19:345–54.PubMedGoogle Scholar
  36. 36.
    Kiguchi K, et al. Characteristic expression of globotriaosyl ceramide in human ovarian carcinomaderived cells with anticancer drug resistance. Cancer Sci. 2006;97:1321–6.PubMedGoogle Scholar
  37. 37.
    Sandvig K, et al. Retrograde transport from the golgi complex to the ER of both Shiga toxin and the nontoxic Shiga B-fragment is regulated by butyric acid and cAMP. J Cell Biol. 1994;126:53–64.PubMedGoogle Scholar
  38. 38.
    Tam P, et al. Differential intracellular trafficking and binding of verotoxin 1 and verotoxin 2 to globotriaosylceramide-containing lipid assemblies. J Cell Physiol. 2008;216:750–63.PubMedGoogle Scholar
  39. 39.
    Burger K, Gimpl G, Fahrenholz F. Regulation of receptor function by cholesterol. Cell Mol Life Sci. 2000;57:1577–92.PubMedGoogle Scholar
  40. 40.
    Chark D, Nutikka A, Trusevych N, Kuzmina J, Lingwood C. Differential carbohydrate epitope recognition of globotriaosyl ceramide by verotoxins and a monoclonal antibody. Eur J Bioch. 2004;271:405–17.Google Scholar
  41. 41.
    Smith DC, et al. The association of Shiga-like toxin with detergent-resistant membranes is modulated by glucosylceramide and is an essential requirement in the endoplasmic reticulum for a cytotoxic effect. Mol Biol Cell. 2006;17:1375–87.PubMedGoogle Scholar
  42. 42.
    Hoey DEE, Currie C, Lingwood CA, Gally DL, Smith DGE. Binding of verotoxin 1 to primary intestinal epithelial cells expressing Gb3 results in trafficking of toxin to lysosomal compartments. Cell Microbiol. 2003;5:85–97.PubMedGoogle Scholar
  43. 43.
    Khine AA, Firtel M, Lingwood CA. CD77-dependent retrograde transport of CD19 to the nuclear membrane: functional relationship between CD77 and CD19 during germinal center B-cell apoptosis. J Cell Physiol. 1998;176:281–92.PubMedGoogle Scholar
  44. 44.
    Maloney MD, Lingwood CA. CD19 Has a potential CD77 (Globotriaosyl ceramide)-binding site with sequence similarity to verotoxin B-subunits: implications of molecular mimicry for B cell adhesion and enterohemorrhagic Escherichia coli pathogenesis. J Exp Med. 1994;180:191–201.PubMedGoogle Scholar
  45. 45.
    Obrig TG, et al. Direct cytotoxic action of Shiga toxin on human vascular endothelial cells. Infect Immun. 1988;56:2373–8.PubMedGoogle Scholar
  46. 46.
    Ohmi K, Kiyokawa N, Takeda T, Fujimoto J. Human microvascular endothelial cells are strongly sensitive to Shiga toxin. Biochem Biophys Res Commun. 1998;251:137–41.PubMedGoogle Scholar
  47. 47.
    Holgersson J, Jovall PA, Breimer ME. Glycosphingolipids of human large intestine: detailed structural characterization with special reference to blood group compounds and bacterial receptor structures. J Biochem. 1991;110:120–31.PubMedGoogle Scholar
  48. 48.
    Schuller S, Frankel G, Phillips AD. Interaction of Shiga toxin from Escherichia coli with human intestinal epithelial cell lines and explants: Stx2 induces epithelial damage in organ culture. Cell Microbiol. 2004;6:289–301.PubMedGoogle Scholar
  49. 49.
    Ramegowda B, Samuel JE, Tesh VL. Interaction of Shiga toxins with human brain microvascular endothelial cells: cytokines as sensitizing agents. J Infect Dis. 1999;180:1205–13.PubMedGoogle Scholar
  50. 50.
    Eisenhauer PE, et al. Tumor necrosis factor alpha increases human cerebral endothelial cell Gb3 and sensitivity to Shiga toxin. Infect Immun. 2001;69:1889–94.PubMedGoogle Scholar
  51. 51.
    Stricklett PK, Hughes AK, Ergonul Z, Kohan DE. Molecular basis for up-regulation by inflammatory cytokines of Shiga toxin 1 cytotoxicity and globotriaosylceramide expression. J Infect Dis. 2002;186:976–82.PubMedGoogle Scholar
  52. 52.
    Ergonul Z, Hughes AK, Kohan DE. Induction of apoptosis of human brain microvascular endothelial cells by Shiga toxin. J Infect Dis. 2003;187:154–8.PubMedGoogle Scholar
  53. 53.
    Uchida H, et al. Shiga toxins induce apoptosis in pulmonary epithelium–derived cells. J Infect Dis. 1999;180:1902–11.PubMedGoogle Scholar
  54. 54.
    Takahashi K, Funata N, Ikuta F, Sato S. Neuronal apoptosis and inflammatory responses in the central nervous system of a rabbit treated with Shiga toxin-2. J Neuroinflamm. 2008;5:11–23.Google Scholar
  55. 55.
    De Rosa MF, et al. Inhibition of multidrug resistance by adamantylgb3, a globotriasylceramide analog. J Biol Chem. 2008;283:4501–11.PubMedGoogle Scholar
  56. 56.
    Bielaszewska M, Karch H. Consequences of enterohaemorrhagic Escherichia coli infection for the vascular endothelium. Thromb Haemost. 2005;94:312–8.PubMedGoogle Scholar
  57. 57.
    Nakao H, Takeda T. Escherichia coli Shiga toxin. J Nat Toxins. 2000;9:299–313.PubMedGoogle Scholar
  58. 58.
    Karch H. The role of virulence factors in enterohemorrhagic Escherichia coli (EHEC)-associated hemolytic: uremic syndrome. Semin Thromb Hemost. 2001;27:207–13.PubMedGoogle Scholar
  59. 59.
    Forsyth KD, et al. Neutrophil-mediated endothelial injury in haemolytic uraemic syndrome. Lancet. 1989;2:411–4.PubMedGoogle Scholar
  60. 60.
    Morigi M, et al. Verotoxin-1-induced up-regulation of adhesive molecules renders microvascular endothelial cells thrombogenic at high shear stress. Blood. 2001;98:1828–35.PubMedGoogle Scholar
  61. 61.
    Ching JC, Jones NL, Ceponis PJ, Karmali MA, Sherman PM. Escherichia coli shiga-like toxins induce apoptosis and cleavage of poly (ADP-ribose) polymerase via in vitro activation of caspases. Infect Immun. 2002;70:4669–77.PubMedGoogle Scholar
  62. 62.
    Kiyokawa N, et al. Activation of the caspase cascade during Stx1-induced apoptosis in Burkitt’s lymphoma cells. J Cell Biochem. 2001;81:128–42.PubMedGoogle Scholar
  63. 63.
    Tétaud C, et al. Two distinct Gb3/CD77 signaling pathways leading to apoptosis are triggered by anti-Gb3/CD77 mAb and verotoxin-1. J Biol Chem. 2003;278:45200–8.PubMedGoogle Scholar
  64. 64.
    Garibal J, Hollville É, Renouf B, Tétaud C, Wiels J. Caspase-8-mediated cleavage of Bid and protein phosphatase 2A-mediated activation of Bax is necessary for Verotoxin-1-induced apoptosis in Burkitt’s lymphoma cells. Cell Signal. 2001;22:467–75.Google Scholar
  65. 65.
    Lee SY, Cherla RP, Caliskan I, Tesh VL. Shiga toxin 1 induces apoptosis in the human myelogenous leukemia cell line THP-1 by a caspase-8-dependent, tumor necrosis factor-independent mechanism. Infect Immun. 2008;73:5115–26.Google Scholar
  66. 66.
    Erwert RD, et al. Shiga toxin induces decreased expression of the anti-apoptotic protein Mcl-1 concomitant with the onset of endothelial apoptosis. Microb Pathog. 2003;35:87–93.PubMedGoogle Scholar
  67. 67.
    Fujii J, et al. Rapid apoptosis induced by Shiga toxin in HeLa cells. Infect Immun. 2003;71:2724–35.PubMedGoogle Scholar
  68. 68.
    Gariepy J. The use of Shiga-like toxin 1 in cancer therapy. Crit Rev Oncol Hematol. 2001;39:99–106.PubMedGoogle Scholar
  69. 69.
    LaCasse EC, et al. Shiga-like toxin-1 receptor on human breast cancer, lymphoma, myeloma and absence from CD34(+) hematopoietic stem cells: implications for ex vivo tumor purging and autologous stem cell transplantation. Blood. 1999;94:2901–10.PubMedGoogle Scholar
  70. 70.
    Salhia B, Rutka JT, Lingwood C, Nutikka A, Van Furth WR. The treatment of malignant meningioma with verotoxin. Neoplasia. 2002;4:304–11.PubMedGoogle Scholar
  71. 71.
    Murray LJ, Habeshaw JA, Wiels J, Greaves MF. Expression of Burkitt lymphoma-associated antigen (defined by the monoclonal antibody 38.13) on both normal and malignant germinal-centre B cells. Int J Cancer. 1985;36:561–5.PubMedGoogle Scholar
  72. 72.
    Ohyama C, et al. Changes in glycolipid expression in human testicular tumor. Int J Cancer. 1990;45:1040–4.PubMedGoogle Scholar
  73. 73.
    Johansson D, et al. Verotoxin-1 induction of apoptosis in Gb3- expressing human glioma cell lines. Cancer Biol Ther. 2006;5:1211–7.PubMedGoogle Scholar
  74. 74.
    Arab S, et al. Expression of the verotoxin receptor glycolipid, globotriaosylceramide, in ovarian hyperplasias. Oncol Res. 1997;9:553–63.PubMedGoogle Scholar
  75. 75.
    Fredman P, Hedberg K, Brezicka T. Gangliosides as therapeutic targets for cancer. BioDrugs. 2003;17:155–67.PubMedGoogle Scholar
  76. 76.
    Kovbasnjuk O, et al. The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancer. Proc Natl Acad Sci USA. 2005;102:19087–92.PubMedGoogle Scholar
  77. 77.
    Johannes L, Decaudin D. Protein toxins: intracellular trafficking for targeted therapy. Gene Ther. 2005;12:1360–8.PubMedGoogle Scholar
  78. 78.
    Janssen KP, et al. In vivo tumor targeting using a novel intestinal pathogen-based delivery approach. Cancer Res. 2006;66:7230–6.PubMedGoogle Scholar
  79. 79.
    Ludwig K, et al. Antibody response to Shiga toxins Stx2 and Stx1 in children with enteropathic hemolytic-uremic syndrome. J Clin Microbiol. 2001;39:2272–9.PubMedGoogle Scholar
  80. 80.
    Levine MM, et al. Antibodies to shiga holotoxin and to two synthetic peptides of the B subunit in sera of patients with Shigella dysenteriae 1 dysentery. J Clin Microbiol. 1992;30:1636–41.PubMedGoogle Scholar
  81. 81.
    O’Brien AD, et al. Shiga toxin: biochemistry, genetics, mode of action, and role in pathogenesis. Curr Top Microbiol Immunol. 1992;180:65–94.PubMedGoogle Scholar
  82. 82.
    Vingert B, et al. The Shiga toxin B-subunit targets antigen in vivo to dendritic cells and elicits anti-tumor immunity. Eur J Immunol. 2006;36:1124–35.PubMedGoogle Scholar
  83. 83.
    Haicheur N, et al. Vt B-subunit of Shiga toxin fused to a tumor antigen elicits CTL and targets dendritic cells to allow MHC class I restricted presentation of peptides derived from exogenous antigens. J Immunol. 2000;165:3301–8.PubMedGoogle Scholar
  84. 84.
    Wang H, Griffiths MN, Burton DR, Ghazal P. Rapid antibody responses by low-dose, single-step, dendritic cell-targeted immunization. Proc Natl Acad Sci USA. 2000;97:847–85.PubMedGoogle Scholar
  85. 85.
    Haicheur N, et al. The B subunit of Shiga toxin coupled to fullsize antigenic protein elicits humoral and cell-mediated immune responses associated with a Th1-dominant polarization. Int Immunol. 2003;15:1–11.Google Scholar
  86. 86.
    Falguières T. Human colorectal tumors and metastases express Gb3 and can be targeted by an intestinal pathogen-based delivery tool. Mol Cancer Ther. 2008;7:2498–508.PubMedGoogle Scholar
  87. 87.
    Viel T, et al. In vivo tumor targeting by the B-subunit of shiga toxin. Mol Imaging. 2008;7:239–47.PubMedGoogle Scholar
  88. 88.
    Rutjes NW, Binnington BA, Smith CR, Maloney MD, Lingwood CA. Differential tissue targeting and pathogenesis of verotoxins 1 and 2 in the mouse animal model. Kidney Int. 2002;62:832–45.PubMedGoogle Scholar
  89. 89.
    Imberty A, Wimmerová M, Mitchell EP, Gilboa-Garber N. Structures of the lectins from Pseudomonas aeruginosa: insight into the molecular basis for host glycan recognition. Microbes Infect. 2004;6:221–8.PubMedGoogle Scholar
  90. 90.
    Blanchard B, et al. Structural basis of the preferential binding for globo-series glycosphingolipids displayed by Pseudomonas aeruginosa lectin I. Mol Biol. 2008;383:837–53.Google Scholar
  91. 91.
    Distler U, et al. Shiga toxin receptor Gb3Cer/CD77: tumor-association and promising therapeutic target in pancreas and colon cancer. PLoS ONE. 2009;4(8):e6813.Google Scholar
  92. 92.
    Schuller S, Heuschkel R, Torrente F, Kaper JB, Phillips AD. Shiga toxin binding in normal and inflamed human intestinal mucosa. Microbes Infect. 2007;9:35–9.PubMedGoogle Scholar
  93. 93.
    Ishitoya S, et al. Verotoxin induces rapid elimination of human renal tumor xenografts in SCID mice. J Urol. 2004;171:1309–13.PubMedGoogle Scholar
  94. 94.
    Arab S, Rutka J, Lingwood C. Verotoxin induces apoptosis and the complete, rapid, long-term elimination of human astrocytoma xenografts in nude mice. Oncol Res. 1999;11:33–9.PubMedGoogle Scholar
  95. 95.
    Heath-Engel HM, Lingwood CA. Verotoxin sensitivity of ECV304 cells in vitro and in vivo in a xenograft tumour model: VT1 as a tumour neovascular marker. Angiogenesis. 2003;6:129–41.PubMedGoogle Scholar
  96. 96.
    Johansson D, et al. Expression of verotoxin-1 receptor Gb3 in breast cancer tissue and verotoxin-1 signal transduction to apoptosis. BMC Cancer. 2009;9:67–76.PubMedGoogle Scholar
  97. 97.
    Bornkamm GW, Polack A, Eick D, Berger R, Lenoir GM. Chromosome translocations and Epstein-Barr virus in Burkitt’s lymphoma. Onkologie. 1987;10:196–204.PubMedGoogle Scholar
  98. 98.
    Jaffe ES, et al. Burkitt’s lymphoma: a single disease with multiple variants. The World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues. Blood. 1999;3:1124.Google Scholar
  99. 99.
    Gordon J, et al. CD40 ligand, Bcl-2, and Bcl-xL spare group I Burkitt lymphoma cells from CD77-directed killing via Verotoxin-1B chain but fail to protect against the holotoxin. Cell Death Differ. 2000;7:785–94.PubMedGoogle Scholar
  100. 100.
    Cohen A, Hannigan GE, Williams BRG, Lingwood CA. Roles of globotriosyl- and galabiosylceramide in verotoxin binding and high affinity interferon receptor. J Biol Chem. 1987;262:17088–91.PubMedGoogle Scholar
  101. 101.
    Wiels J, Fellous M, Tursz T. Monoclonal antibody against a Burkitt lymphoma associated antigen. Proc Natl Acad Sci USA. 1981;78:6485–9.PubMedGoogle Scholar
  102. 102.
    Sakthivel R, Christensson B, Ehlin-Henriksson B, Klein G. Immunophenotypic characterization of follicle-center-cell-derived non-Hodgkin’s lymphomas. Int J Cancer. 1989;43:624–30.PubMedGoogle Scholar
  103. 103.
    Taga S, et al. Intracellular signalling events in CD77-mediated apoptosis of Burkitt’s lymphoma cells. Blood. 1997;90:2757–67.PubMedGoogle Scholar
  104. 104.
    Grafton G, Goodall M, Gregory CD, Gordon J. Mechanisms of antigen receptor-dependent apoptosis in human B lymphoma cell lines probed with a panel of 27 monoclonal antibodies. Cell Immunol. 1997;182:45–56.PubMedGoogle Scholar
  105. 105.
    Michael JM, Lavin MF, Watters DJ. Resistance to radiation-induced apoptosis in Burkitt’s lymphoma cells is associated with defective ceramide signaling. Cancer Res. 1997;57:3600–5.PubMedGoogle Scholar
  106. 106.
    Furukawa K, et al. Expression of the Gb3/CD77 synthase gene in megakaryoblastic leukemia cells. J Biol Chem. 2002;277:11247–54.PubMedGoogle Scholar
  107. 107.
    Zhang X-g, et al. Reproducible obtaining of human myeloma cell lines as a model for tumor stem cell study in human multiple myeloma. Blood. 1994;83:3654–63.PubMedGoogle Scholar
  108. 108.
    Szczepek AJ, et al. A high frequency of circulating B cells share clonotypic IgH VDJ rearrangements with autologous bone marrow plasma cells in multiple myeloma, as measured by single cell and in situ RT-PCR. Blood. 1998;92:2844–55.PubMedGoogle Scholar
  109. 109.
    Bechtel D, Kurth J, Unkel C, Ku¨ppers R. Transformation of BCR-deficient germinal-center B cells by EBV supports a major role of the virus in the pathogenesis of Hodgkin and posttransplantation lymphomas. Blood. 2005;106:4345–50.PubMedGoogle Scholar
  110. 110.
    Arbus GS, et al. Verotoxin targets lymphoma infiltrates of patients with post-transplant lymphoproliferative disease. Leukemia Res. 2000;24:857–64.Google Scholar
  111. 111.
    Craxton A, Chuang PI, Shu G, Harlan JM, Clark EA. The CD40-inducible Bcl-2 family member A1 protects B Cells from antigen receptor-mediated apoptosis. Cell Immunol. 2000;200:56–62.PubMedGoogle Scholar
  112. 112.
    Li T, Ramirez K, Palacios R. Distinct patterns of Fas cell surface expression during development of T- or B-lymphocyte lineages in normal, scid, and mutant mice lacking or overexpressing p53, bcl-2, or rag-2 genes. Cell Growth Differ. 1996;7:107–14.PubMedGoogle Scholar
  113. 113.
    Ghia P, et al. Unbalanced expression of Bcl-2 family proteins in follicular lymphoma: contribution of CD40 signaling in promoting survival. Blood. 1998;91:224–51.Google Scholar
  114. 114.
    Holder MJ, et al. Suppression of apoptosis in normal and neoplastic human B lymphocytes by CD40 ligand is independent of Bcl-2 induction. Eur J Immunol. 1993;23:2368–71.PubMedGoogle Scholar
  115. 115.
    Traulle C, Coiffier B. Evolving role of rituximab in the treatment of patients with non-Hodgkin’s lymphoma. Future Oncol. 2005;1:297–306.PubMedGoogle Scholar
  116. 116.
    Béniguel L, et al. identification of germinal center B cells in blood from HIV-infected drug-naive individuals in central Africa. Clin Dev Immunol. 2004;11:23–7.PubMedGoogle Scholar
  117. 117.
    Ramkumar S, Sakac D, Binnington B, Branch DR, Lingwood CA. Induction of HIV-1 resistance: cell susceptibility to infection is an inverse function of globotriaosyl ceramide levels. Glycobiology. 2009;19:76–82.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • D. Đevenica
    • 1
    Email author
  • V. Čikeš Čulić
    • 2
  • A. Vuica
    • 3
  • A. Markotić
    • 2
  1. 1.University of Split School of MedicineSplitCroatia
  2. 2.Department of Medical Chemistry and BiochemistryUniversity of Split School of MedicineSplitCroatia
  3. 3.University Hospital SplitSplitCroatia

Personalised recommendations