Biochemistry (Moscow)

, Volume 80, Issue 7, pp 808–819 | Cite as

Gangliosides in breast cancer: New perspectives

  • S. Groux-DegrooteEmail author
  • Y. GuérardelEmail author
  • S. JulienEmail author
  • P. DelannoyEmail author


Abstract—Gangliosides are essential compounds of the plasma membrane involved in cell adhesion, proliferation, and recognition processes, as well as in the modulation of signal transduction pathways. These functions are mainly supported by the glycan moiety, and changes in the structure of gangliosides occur under pathological conditions including cancers. With progress in mass spectrometric analysis of gangliosides, the role of gangliosides in breast cancer progression was recently demonstrated. In this review, we summarize current knowledge on the biosynthesis of gangliosides and of the role of disialogangliosides in triple-negative breast cancer progression and metastasis. New perspectives in breast cancer therapy targeting gangliosides are also discussed.


gangliosides breast cancer mass spectrometry metastasis c-Met GD3 synthase 



2,5-dihydroxybenzoic acid


estrogen receptor


electrospray ionization






high-performance liquid chromatography


imaging mass spectrometry


monoclonal antibodies


matrix-associated laser desorption-ionization


mass spectrometry


short hairpin RNA


small interfering RNA


thin layer chromatography


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  1. 1.
    Hakomori, S. I. (2002) The glycosynapse, Proc. Natl. Acad. Sci. USA, 99, 225–232.PubMedCentralCrossRefGoogle Scholar
  2. 2.
    Regina Todeschini, A., and Hakomori, S. I. (2008) Functional role of glycosphingolipids and gangliosides in control of cell adhesion, motility, and growth, through glycosynaptic microdomains, Biochim. Biophys. Acta, 1780, 421–433.PubMedCrossRefGoogle Scholar
  3. 3.
    Birkle, S., Zeng, G., Gao, L., Yu, R. K., and Aubry, J. (2003) Role of tumor-associated gangliosides in cancer progression, Biochimie, 85, 455–463.PubMedCrossRefGoogle Scholar
  4. 4.
    Prokazova, N. V., and Bergelson, L. D. (1994) Gangliosides and atherosclerosis, Lipids, 29, 1–5.PubMedCrossRefGoogle Scholar
  5. 5.
    Ariga, T, McDonald, M. P., and Yu, R. K. (2008) Role of ganglioside metabolism in the pathogenesis of Alzheimer’s disease- a review, J. Lipid Res., 49, 1157–1175.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Furukawa, K., Hamamura, K., Aixinjueluo, W., and Furukawa, K. (2006) Biosignals modulated by tumor-associated carbohydrate antigens: novel targets for cancer therapy, Ann. N. Y. Acad. Sci., 1086, 185–198.PubMedCrossRefGoogle Scholar
  7. 7.
    Krengel, U., and Bousquet, P. A. (2014) Molecular recognition of gangliosides and their potential for cancer immunotherapies, Front. Immunol., 5, 325.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Rabu, C., McIntosh, R., Jurasova, Z., and Durrant, L. (2012) Glycans as targets for therapeutic antitumor antibodies, Future Oncol., 8, 943–960.PubMedCrossRefGoogle Scholar
  9. 9.
    Yu, R. K., Yanagisawa, M., and Ariga, T (2007) Glycosphingolipid structures, in Comprehensive Glycoscience (Kamerling, H., ed.) Elsevier, Oxford, UK, pp. 73–122.Google Scholar
  10. 10.
    Ichikawa, S., Sakiyama, H., Suzuki, G., Hidari, K. I., and Hirabayashi, Y (1996) Expression cloning of a cDNA for human ceramide glucosyltransferase that catalyzes the first glycosylation step of glycosphingolipid synthesis, Proc. Natl. Acad. Sci. USA, 93, 4638–4643.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Abe, A., Inokuchi, J., Jimbo, M., Shimeno, H., Nagamatsu, A., Shayman, J. A., Shukla, G. S., and Radin, N. S. (1992) Improved inhibitors of glucosylceramide synthase, J. Biochem., 111, 191–196.PubMedGoogle Scholar
  12. 12.
    Nomura, T, Takizawa, M., Aoki, J., Arai, H., Inoue, K., Wakisaka, E., Yoshizuka, N., Imokawa, G., Dohmae, N., Takio, K., Hattori, M., and Matsuo, N. (1998) J. Biol. Chem., 273, 13570–13577.PubMedCrossRefGoogle Scholar
  13. 13.
    Takizawa, M., Nomura, T, Wakisaka, E., Yoshizuka, N., Aoki, J., Arai, H., Inoue, K., Hattori, M., and Matsuo, N. (1999) cDNA cloning and expression of human lactosylceramide synthase, Biochim. Biophys. Acta, 1438, 301–304.PubMedCrossRefGoogle Scholar
  14. 14.
    Zeng, G., and Yu, R. K. (2008) Cloning and transcriptional regulation of genes responsible for synthesis of gangliosides, Curr. Drug Targets, 9, 317–324.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Ishii, A., Ohta, M., Watanabe, Y, Matsuda, K., Ishiyama, K., Sakoe, K., Nakamura, M., Inokuchi, J., Sanai, Y, and Saito, M. (1998) Expression cloning and functional characterization of human cDNA for ganglioside GM3 synthase, J. Biol. Chem., 273, 31652–31655.PubMedCrossRefGoogle Scholar
  16. 16.
    Haraguchi, M., Yamashiro, S., Yamamoto, A., Furukawa, K., Takamiya, K., Lloyd, K. O., Shiku, H., and Furukawa, K. (1994) Isolation of GD3 synthase gene by expression cloning of GM3 alpha-2,8-sialyltransferase cDNA using anti-GD2 monoclonal antibody, Proc. Natl. Acad. Sci. USA, 91, 10455–10459.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Nakayama, J., Fukuda, M. N., Hirabayashi, Y, Kanamori, A., Sasaki, K., Nishi, T, and Fukuda, M. (1996) Expression cloning of a human GT3 synthase. GD3 and GT3 are synthesized by a single enzyme, J. Biol. Chem., 271, 3684–3691.PubMedCrossRefGoogle Scholar
  18. 18.
    Kim, Y. J., Kim, K. S., Do, S., Kim, C. H., Kim, S. K., and Lee, Y. C. (1997) Molecular cloning and expression of human alpha2,8-sialyltransferase (hST8Sia V), Biochem. Biophys. Res. Commun., 235, 327–330.PubMedCrossRefGoogle Scholar
  19. 19.
    Svennerholm, L. (1980) Ganglioside designation, Adv. Exp. Med. Biol., 125, 11.PubMedCrossRefGoogle Scholar
  20. 20.
    Nagata, Y, Yamashiro, S., Yodoi, J., Lloyd, K. O., Shiku, H., and Furukawa, K. (1992) Expression cloning of beta- I,4-N-acetylgalactosaminyltransferase cDNAs that determine the expression of GM2 and GD2 gangliosides, J. Biol. Chem., 267, 12082–12089.PubMedGoogle Scholar
  21. 21.
    Amado, M., Almeida, R., Carneiro, F., Levery, S. B., Holmes, E. H., Nomoto, M., Hollingsworth, M. A., Hassan, H., Schwientek, T, Nielsen, P. A., Bennett, E. P., and Clausen, H. (1998) A family of human beta3-galactosyltransferases. Characterization of four members of a UDP-galactose:beta-N-acetyl-glucosamine/beta-N-acetylgalactosamine/ beta-1,3-galactosyltransferase family, J. Biol. Chem., 273, 12770–12778.PubMedCrossRefGoogle Scholar
  22. 22.
    Iber, H., Zacharias, C., and Sandhoff, K. (1992) The cseries gangliosides GT3, GT2, and GP1c are formed in rat liver Golgi by the same set of glycosyltransferases that catalyze the biosynthesis of asialo-, a- and b-series gangliosides, Glycobiology, 2, 137–142.PubMedCrossRefGoogle Scholar
  23. 23.
    Yamashiro, S., Haraguchi, M., Furukawa, K., Takamiya, K., Yamamoto, A., Nagata, Y, Lloyd, K. O., Shiku, H., and Furukawa, K. (1995) Substrate specificity of beta 1,4- N-acetylgalactosaminyltransferase in vitro and in cDNAtransfected cells. GM2/GD2 synthase efficiently generates asialo-GM2 in certain cells, J. Biol. Chem., 270, 61496155.Google Scholar
  24. 24.
    Kitagawa, H., and Paulson, J. C. (1994) Cloning of a novel alpha 2,3-sialyltransferase that sialylates glycoprotein and glycolipid carbohydrate groups, J. Biol. Chem., 269, 13941401.Google Scholar
  25. 25.
    Giordanengo, V., Bannwarth, S., Laffont, C., Van Miegem, V., Harduin-Lepers, A., Delannoy, P., and Lefebvre, J. C. (1997) Cloning and expression of cDNA for a human Gal(beta1-3)GalNAc alpha2,3-sialyltransferase from the CEM T-cell line, Eur. J. Biochem., 247, 558–566.PubMedCrossRefGoogle Scholar
  26. 26.
    Sturgill, E. R., Aoki, K., Lopez, P. H., Colacurcio, D., Vajn, K., Lorenzini, I., Majic, S., Yang, W. H., Heffer, M., Tiemeyer, M., Marth, J. D., and Schnaar, R. L. (2012) Biosynthesis of the major brain gangliosides GD1a and GT1b, Glycobiology, 22, 1289–1301.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Harduin-Lepers, A. (2013) Vertebrate sialyltransferases, in Sialobiology: Structure, Biosynthesis and Function of Sialic Acid Glycoconjugates in Health and Disease (Tiralongo, J., and Martinez-Duncker, J. T, eds.) Bentham Science Publishers, pp. 139–187.Google Scholar
  28. 28.
    Okajima, T, Fukumoto, S., Ito, H., Kiso, M., Hirabayashi, Y, Urano, T, and Furukawa, K. (1999) Molecular cloning of brain-specific GD1alpha synthase (ST6GalNAc V) containing CAG/Glutamine repeats, J. Biol. Chem., 274, 30557–30562.PubMedCrossRefGoogle Scholar
  29. 29.
    Bobowski, M., Cazet, A., Steenackers, A., and Delannoy, P. (2012) Role of complex gangliosides in cancer progression, Carbohydr. Chem., 37, 1–20.Google Scholar
  30. 30.
    Giraudo, C. G., and Maccioni, H. J. (2003) Ganglioside glycosyltransferases organize in distinct multienzyme complexes in CHO-K1 cells, J. Biol. Chem., 278, 40262–40271.PubMedCrossRefGoogle Scholar
  31. 31.
    Hidari, J. K., Ichikawa, S., Furukawa, K., Yamasaki, M., and Hirabayashi, Y. (1994) beta-1-4-N-acetylgalactosaminyltransferase can synthesize both asialoglycosphingolipid GM2 and glycosphingolipid GM2 in vitro and in vivo: isolation and characterization of a beta-1-4-N-acetylgalactosaminyltransferase cDNA clone from rat ascites hepatoma cell line AH7974F, Biochem. J., 303, 957–965.PubMedCentralPubMedGoogle Scholar
  32. 32.
    Schnaar, R. L. (1994) Isolation of glycosphingolipids, Methods Enzymol., 230, 348–370.PubMedCrossRefGoogle Scholar
  33. 33.
    Hakomori, S. I. (1983) Chemistry of glycosphingolipids, in Sphingolipid Biochemistry- Handbook of Lipid Research (Kanfer, J. N., and Hakomori, S. I., eds.) Plenum Press, New York, pp. 1–165.Google Scholar
  34. 34.
    Svennerholm, L., and Fredman, P. (1980) A procedure for the quantitative isolation of brain gangliosides, Biochim. Biophys. Acta, 617, 97–109.PubMedCrossRefGoogle Scholar
  35. 35.
    Ijuin, T, Kitajima, K., Song, Y, Kitazume, S., Inoue, S., Haslam, S. M., Morris, H. R., Dell, A., and Inoue, Y (1996) Isolation and identification of novel sulfated and nonsulfated oligosialylglycosphingolipids from sea urchin sperm, Glycoconj. J., 13, 401–413.PubMedCrossRefGoogle Scholar
  36. 36.
    Powell, A. K., and Harvey, D. J. (1996) Stabilization of sialic acids in N-linked oligosaccharides and gangliosides for analysis by positive ion matrix-assisted laser desorption/ionization mass spectrometry, Rapid Commun. Mass Spectrom., 10, 1027–1032.PubMedCrossRefGoogle Scholar
  37. 37.
    Wheeler, S. F., Domann, P., and Harvey, D. J. (2009) Derivatization of sialic acids for stabilization in matrixassisted laser desorption/ionization mass spectrometry and concomitant differentiation of alpha(2 3)- and alpha(2 6)-isomers, Rapid Commun. Mass Spectrom., 23, 303–312.PubMedCrossRefGoogle Scholar
  38. 38.
    Liang, Y. J., Kuo, H. H., Lin, C. H., Chen, Y. Y, Yang, B. C., Cheng, Y. Y, Yu, A. L., Khoo, K. H., and Yu, J. (2010) Switching of the core structures of glycosphingolipids from globo- and lacto- to ganglio-series upon human embryonic stem cell differentiation, Proc. Natl. Acad. Sci. USA, 107, 22564–22569.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Boccuto, L., Aoki, K., Flanagan-Steet, H., Chen, C. F., Fan, X., Bartel, F., Petukh, M., Pittman, A., Saul, R., Chaubey, A., Alexov, E., Tiemeyer, M., Steet, R., and Schwartz, C. E. (2014) A mutation in a ganglioside biosynthetic enzyme, ST3GAL5, results in salt and pepper syndrome, a neurocutaneous disorder with altered glycolipid and glycoprotein glycosylation, Hum. Mol. Genet., 23, 418433.CrossRefGoogle Scholar
  40. 40.
    Lee, D., and Cha, S. (2014) 5-Methoxysalicylic acid matrix for ganglioside analysis with matrix-assisted laser desorption/ ionization mass spectrometry, J. Am. Soc. Mass Spectrom., Dec 11, Epub ahead of print.Google Scholar
  41. 41.
    Colsch, B., and Woods, A. S. (2010) Localization and imaging of sialylated glycosphingolipids in brain tissue sections by MALDI mass spectrometry, Glycobiology, 20, 661667.CrossRefGoogle Scholar
  42. 42.
    Mank, M., Stahl, B., and Boehm, G. (2004) 2,5- Dihydroxybenzoic acid butylamine and other ionic liquid matrixes for enhanced MALDI-MS analysis of biomolecules, Anal. Chem., 76, 2938–2950.PubMedCrossRefGoogle Scholar
  43. 43.
    Sugiura, Y, Shimma, S., Konishi, Y, Yamada, M. K., and Setou, M. (2008) Imaging mass spectrometry technology and application on ganglioside study; visualization of agedependent accumulation of C20-ganglioside molecular species in the mouse hippocampus, PLoS One, 3, e3232.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Chan, K., Lanthier, P., Liu, X., Sandhu, J. K., Stanimirovic, D., and Li, J. (2009) MALDI mass spectrometry imaging of gangliosides in mouse brain using ionic liquid matrix, Anal. Chim. Acta, 639, 57–61.PubMedCrossRefGoogle Scholar
  45. 45.
    Goto-Inoue, N., Hayasaka, T, Zaima, N., Kashiwagi, Y, Yamamoto, M., Nakamoto, M., and Setou, M. (2010) The detection of glycosphingolipids in brain tissue sections by imaging mass spectrometry using gold nanoparticles, J. Am. Soc. Mass Spectrom., 21, 1940–1943.PubMedGoogle Scholar
  46. 46.
    Richards, A. L., Lietz, C. B., Wager-Miller, J., Mackie, K., and Trimpin, S. (2012) Localization and imaging of gangliosides in mouse brain tissue sections by laserspray ionization inlet, J. Lipid Res., 53, 1390–1398.PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Whitehead, S. N., Chan, K. H., Gangaraju, S., Slinn, J., Li, J., and Hou, S. T (2011) Imaging mass spectrometry detection of gangliosides species in the mouse brain following transient focal cerebral ischemia and long-term recovery, PLoS One, 6, e20808.PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Snel, M. F., and Fuller, M. (2010) High-spatial resolution matrix-assisted laser desorption ionization imaging analysis of glucosylceramide in spleen sections from a mouse model of Gaucher disease, Anal. Chem., 82, 3664–3670.PubMedCrossRefGoogle Scholar
  49. 49.
    Kettling, H., Vens-Cappell, S., Soltwisch, J., Pirkl, A., Haier, J., Müthing, J., and Dreisewerd, K. (2014) MALDI mass spectrometry imaging of bioactive lipids in mouse brain with a Synapt G2-S mass spectrometer operated at elevated pressure: improving the analytical sensitivity and the lateral resolution to ten micrometers, Anal. Chem., 86, 7798–7805.PubMedCrossRefGoogle Scholar
  50. 50.
    Cheng, S. C., Huang, M. Z., and Shiea, J. (2011) Thin layer chromatography/mass spectrometry, J. Chromatogr. A, 1218, 2700–2711.PubMedCrossRefGoogle Scholar
  51. 51.
    Mlinac, K., Fabris, D., Vukelic, Z., Rozman, M., Heffer, M., and Bognar, S. K. (2013) Structural analysis of brain ganglioside acetylation patterns in mice with altered ganglioside biosynthesis, Carbohydr. Res., 382, 1–8.PubMedCrossRefGoogle Scholar
  52. 52.
    Suzuki, A., Miyazaki, M., Matsuda, J., and Yoneshige, A. (2011) High-performance thin-layer chromatography/ mass spectrometry for the analysis of neutral glycosphingolipids, Biochim. Biophys. Acta, 1811, 861–874.PubMedCrossRefGoogle Scholar
  53. 53.
    Miyazaki, M., Yonesige, A., Matsuda, J., Kuroda, Y, Kojima, N., and Suzuki, A. (2008) High-performance thin-layer chromatography/mass spectrometry for rapid analysis of neutral glycosphingolipids, J. AOAC Int., 91, 1218–1226.PubMedGoogle Scholar
  54. 54.
    Valdes-Gonzalez, T, Goto-Inoue, N., Hirano, W., Ishiyama, H., Hayasaka, T, Setou, M., and Taki, T (2011) New approach for glyco- and lipidomics- molecular scanning of human brain gangliosides by TLC-Blot and MALDI-QIT-TOF MS, J. Neurochem., 116, 678683.CrossRefGoogle Scholar
  55. 55.
    Ivleva, V. B., Elkin, Y. N., Budnik, B. A., Moyer, S. C., O’Connor, P. B., and Costello, C. E. (2004) Coupling thinlayer chromatography with vibrational cooling matrixassisted laser desorption/ionization Fourier transform mass spectrometry for the analysis of ganglioside mixtures, Anal. Chem., 76, 6484–6491.PubMedCrossRefGoogle Scholar
  56. 56.
    Ivleva, V. B., Sapp, L. M., O’Connor, P. B., and Costello, C. E. (2005) Ganglioside analysis by thin-layer chromatography matrix-assisted laser desorption/ionization orthogonal time-of-flight mass spectrometry, J. Am. Soc. Mass Spectrom., 16, 1552–1560.PubMedCrossRefGoogle Scholar
  57. 57.
    Park, H., Zhou, Y, and Costello, C. E. (2014) Direct analysis of sialylated or sulfated glycosphingolipids and other polar and neutral lipids using TLC-MS interfaces, J. Lipid Res., 55, 773–781.PubMedCentralPubMedCrossRefGoogle Scholar
  58. 58.
    Sorensen, L. K. (2006) A liquid chromatography/tandem mass spectrometric approach for the determination of gangliosides GD3 and GM3 in bovine milk and infant formulae, Rapid Commun. Mass Spectrom., 20, 3625–3633.PubMedCrossRefGoogle Scholar
  59. 59.
    Fuller, M., Duplock, S., Hein, L. K., Rigat, B. A., and Mahuran, D. J. (2014) Liquid chromatography/electrospray ionization-tandem mass spectrometry quantification of GM2 gangliosides in human peripheral cells and plasma, Anal. Biochem., 458, 20–26.PubMedCrossRefGoogle Scholar
  60. 60.
    Fong, B., Norris, C., Lowe, E., and McJarrow, P. (2009) Liquid chromatography-high-resolution mass spectrometry for quantitative analysis of gangliosides, Lipids, 44, 867874.CrossRefGoogle Scholar
  61. 61.
    Lee, H., Lerno, L. A., Jr., Choe, Y, Chu, C. S., Gillies, L. A., Grimm, R., Lebrilla, C. B., and German, J. B. (2012) Multiple precursor ion scanning of gangliosides and sulfatides with a reversed-phase microfluidic chip and quadrupole time-of-flight mass spectrometry, Anal. Chem., 84, 5905–5912.PubMedCentralPubMedCrossRefGoogle Scholar
  62. 62.
    Zhang, J., Ren, Y, Huang, B., Tao, B., Pedersen, M. R., and Li, D. (2012) Determination of disialoganglioside GD3 and monosialoganglioside GM3 in infant formulas and whey protein concentrates by ultra-performance liquid chromatography/electrospray ionization tandem mass spectrometry, J. Sep. Sci., 35, 937–946.PubMedCrossRefGoogle Scholar
  63. 63.
    Steenackers, A., Vanbeselaere, J., Cazet, A., Bobowski, M., Rombouts, Y, Colomb, F, Le Bourhis, X., Guerardel, Y, and Delannoy, P. (2012) Accumulation of unusual gangliosides G(Q3) and G(P3) in breast cancer cells expressing the G(D3) synthase, Molecules, 17, 9559–9572.PubMedCrossRefGoogle Scholar
  64. 64.
    Nara, K., Watanabe, Y, Kawashima, I., Tai, T, Nagai, Y, and Sanai, Y (1996) Acceptor substrate specificity of a cloned GD3 synthase that catalyzes the biosynthesis of both GD3 and GD1c/GT1a/GQ1b, Eur. J. Biochem., 238, 647–652.PubMedCrossRefGoogle Scholar
  65. 65.
    Nara, K., Watanabe, Y, Maruyama, K., Kasahara, K., Nagai Y, and Sanai, Y. (1994) Expression cloning of a CMP-NeuAc:NeuAc alpha 2-3Gal beta 1-4Glc beta 1- 1'Cer alpha 2,8-sialyltransferase (GD3 synthase) from human melanoma cells, Proc. Natl. Acad. Sci. USA, 91, 7952–7956.PubMedCentralPubMedCrossRefGoogle Scholar
  66. 66.
    Sasaki, K., Kurata, K., Kojima, N., Kurosawa, N., Ohta, S., Hanai, N., Tsuji, S., and Nishi, T (1994) Expression cloning of a GM3-specific alpha-2,8-sialyltransferase (GD3 synthase), J. Biol. Chem., 269, 15950–15956.PubMedGoogle Scholar
  67. 67.
    Furukawa, K., Horie, M., Okutomi, K., Sugano, S., and Furukawa, K. (2003) Isolation and functional analysis of the melanoma specific promoter region of human GD3 synthase gene, Biochim. Biophys. Acta, 1627, 71–78.PubMedCrossRefGoogle Scholar
  68. 68.
    Yamamoto, A., Haraguchi, M., Yamashiro, S., Fukumoto, S., Furukawa, K., Takamiya, K., Atsuta, M., Shiku, H., and Furukawa, K. (1996) Heterogeneity in the expression pattern of two ganglioside synthase genes during mouse brain development, J. Neurochem., 66, 26–34.PubMedCrossRefGoogle Scholar
  69. 69.
    Yu, R. K., Macala, L. J., Taki, T., Weinfield, H. M., and Yu, F S. (1988) Developmental changes in ganglioside composition and synthesis in embryonic rat brain, J. Neurochem., 50, 1825–1829.PubMedCrossRefGoogle Scholar
  70. 70.
    Kang, N. Y, Kim, C. H., Kim, K. S., Ko, J. H., Lee, J. H., Jeong, Y. K., and Lee, Y C. (2007) Expression of the human CMP-NeuAc:GM3 alpha2,8-sialyltransferase (GD3 synthase) gene through the NF-kappaB activation in human melanoma SK-MEL-2 cells, Biochim. Biophys. Acta, 1769, 622–630.PubMedCrossRefGoogle Scholar
  71. 71.
    Dae, H. M., Kwon, H. Y., Kang, N. Y, Song, N. R., Kim, K. S., Kim, C. H., Lee, J. H., and Lee, Y. C. (2009) Isolation and functional analysis of the human glioblastoma- specific promoter region of the human GD3 synthase (hST8Sia I) gene, Acta Biochim. Biophys. Sin. (Shanghai), 41, 237–245.CrossRefGoogle Scholar
  72. 72.
    Marquina, G., Waki, H., Fernandez, L. E., Kon, K., Carr, A., Valiente, O., Perez, R., and Ando, S. (1996) Gangliosides expressed in human breast cancer, Cancer Res., 56, 5165–5171.PubMedGoogle Scholar
  73. 73.
    Oliva, J. P., Valdes, Z., Casaco, A., Pimentel, G., Gonzalez, J., Alvarez, I., Osorio, M., Velazco, M., Figueroa, M., Ortiz, R., Escobar, X., Orozco, M., Cruz, J., Franco, S., Diaz, M., Roque, L., Carr, A., Vazquez, A. M., Mateos, C., Rubio, M. C., Perez, R., and Fernandez, L. E. (2006) Clinical evidences of GM3 (NeuGc) ganglioside expression in human breast cancer using the 14F7 monoclonal antibody labelled with (99m)Tc, Breast Cancer Res. Treat., 96, 115–121.PubMedCrossRefGoogle Scholar
  74. 74.
    Ruckhaberle, E., Rody, A., Engels, K., Gaetje, R., von Minckwitz, G., Schiffmann, S., Grosch, S., Geisslinger, G., Holtrich, U., Karn, T, and Kaufmann, M. (2008) Microarray analysis of altered sphingolipid metabolism reveals prognostic significance of sphingosine kinase 1 in breast cancer, Breast Cancer Res. Treat., 112, 41–52.PubMedCrossRefGoogle Scholar
  75. 75.
    Ruckhaberle, E., Karn, T, Rody, A., Hanker, L., Gatje, R., Metzler, D., Holtrich, U., and Kaufmann, M. (2009) Gene expression of ceramide kinase, galactosyl ceramide synthase and ganglioside GD3 synthase is associated with prognosis in breast cancer, J. Cancer Res. Clin. Oncol., 135, 1005–1013.PubMedCrossRefGoogle Scholar
  76. 76.
    Carcel-Trullols, J., Stanley, J. S., Saha, R., Shaaf, S., Bendre, M. S., Monzavi-Karbassi, B., Suva, L. J., and Kieber-Emmons, T. (2006) Characterization of the glycosylation profile of the human breast cancer cell line, MDA- 231, and a bone colonizing variant, Int. J. Oncol., 28, 11731183.Google Scholar
  77. 77.
    Gu, Y, Zhang, J., Mi, W., Yang, J., Han, F., Lu, X., and Yu, W (2008) Silencing of GM3 synthase suppresses lung metastasis of murine breast cancer cells, Breast Cancer Res., 10, R1.PubMedCentralPubMedCrossRefGoogle Scholar
  78. 78.
    Cazet, A., Groux-Degroote, S., Teylaert, B., Kwon, K. M., Lehoux, S., Slomianny, C., Kim, C. H., Le Bourhis, X., and Delannoy, P. (2009) GD3 synthase overexpression enhances proliferation and migration of MDA-MB-231 breast cancer cells, Biol. Chem., 390, 601–609.PubMedCrossRefGoogle Scholar
  79. 79.
    Cazet, A., Lefebvre, J., Adriaenssens, E., Julien, S., Bobowski, M., Grigoriadis, A., Tutt, A., Tulasne, D., Le Bourhis, X., and Delannoy, P. (2010) GD3 synthase expression enhances proliferation and tumor growth of MDAMB- 231 breast cancer cells through c-Met activation, Mol. Cancer Res., 8, 1526–1535.PubMedCrossRefGoogle Scholar
  80. 80.
    Cazet, A., Bobowski, M., Rombouts, Y, Lefebvre, J., Steenackers, A., Popa, I., Guerardel, Y, Le Bourhis, X., Tulasne, D., and Delannoy, P. (2012) The ganglioside G(D2) induces the constitutive activation of c-Met in MDA-MB-231 breast cancer cells expressing the G(D3) synthase, Glycobiology, 22, 806–816.PubMedCrossRefGoogle Scholar
  81. 81.
    Battula, V. L., Shi, Y, Evans, K. W., Wang, R. Y, Spaeth, E. L., Jacamo, R. O., Guerra, R., Sahin, A. A., Marini, F. C., Hortobagyi, G., Mani, S. A., and Andreeff, M. (2012) Ganglioside GD2 identifies breast cancer stem cells and promotes tumorigenesis, J. Clin. Invest., 122, 2066–2078.PubMedCentralPubMedCrossRefGoogle Scholar
  82. 82.
    Liang, Y. J., Ding, Y, Levery, S. B., Lobaton, M., Handa, K., and Hakomori, S. I. (2013) Differential expression profiles of glycosphingolipids in human breast cancer stem cells vs. cancer non-stem cells, Proc. Natl. Acad. Sci. USA, 110, 4968–4973.PubMedCentralPubMedCrossRefGoogle Scholar
  83. 83.
    Sarkar, T R., Battula, V. L., Werden, S. J., Vijay, G. V., Ramirez-Pena, E. Q., Taube, J. H., Chang, J. T, Miura, N., Porter, W, Sphyris, N., Andreeff, M., and Mani, S. A. (2015) GD3 synthase regulates epithelial-mesenchymal transition and metastasis in breast cancer, Oncogene, 34, 2958–2967.PubMedCrossRefGoogle Scholar
  84. 84.
    Taki, T, Hirabayashi, Y, Ishikawa, H., Ando, S., Kon, K., Tanaka, Y, and Matsumoto, M. (1986) A ganglioside of rat ascites hepatoma AH 7974F cells. Occurrence of a novel disialoganglioside (GD1 alpha) with a unique N-acetylneuraminosyl( alpha 2-6)-N-acetylgalactosamine structure, J. Biol. Chem., 261, 3075–3078.PubMedGoogle Scholar
  85. 85.
    Hirabayashi, Y, Hyogo, A., Nakao, T, Tsuchiya, K., Suzuki, Y, Matsumoto, M., Kon, K., and Ando, S. (1990) Isolation and characterization of extremely minor gangliosides, GM1b and GD1 alpha, in adult bovine brains as developmentally regulated antigens, J. Biol. Chem., 265, 8144–8151.PubMedGoogle Scholar
  86. 86.
    Furuya, S., Irie, F., Hashikawa, T, Nakazawa, K., Kozakai, A., Hasegawa, A., Sudo, K., and Hirabayashi, Y (1994) Ganglioside GD1 alpha in cerebellar Purkinje cells. Its specific absence in mouse mutants with Purkinje cell abnormality and altered immunoreactivity in response to conjunctive stimuli causing long-term desensitization, J. Biol. Chem., 269, 32418–32425.PubMedGoogle Scholar
  87. 87.
    Ikehara, Y., Shimizu, N., Kono, M., Nishihara, S., Nakanishi, H., Kitamura, T, Narimatsu, H., Tsuji, S., and Tatematsu, M. (1999) A novel glycosyltransferase with a polyglutamine repeat; a new candidate for GD1alpha synthase (ST6GalNAc V), FEBSLett., 463, 92–96.CrossRefGoogle Scholar
  88. 88.
    Kroes, R. A., He, H., Emmett, M. R., Nilsson, C. L., Leach, F. E., Amster, I. J., Marshall, A. G., and Moskal, J. R. (2010) Overexpression of ST6GalNAcV, a ganglioside-specific alpha2,6-sialyltransferase, inhibits glioma growth in vivo, Proc. Natl. Acad. Sci. USA, 107, 12646–12651.PubMedCentralPubMedCrossRefGoogle Scholar
  89. 89.
    Taki, T, Ishikawa, D., Ogura, M., Nakajima, M., and Handa, S. (1997) Ganglioside GD1alpha functions in the adhesion of metastatic tumor cells to endothelial cells of the target tissue, Cancer Res., 57, 1882–1888.PubMedGoogle Scholar
  90. 90.
    Bos, P. D., Zhang, X. H., Nadal, C., Shu, W, Gomis, R. R., Nguyen, D. X., Minn, A. J., van de Vijver, M. J., Gerald, W L., Foekens, J. A., and Massague, J. (2009) Genes that mediate breast cancer metastasis to the brain, Nature, 459, 1005–1009.PubMedCentralPubMedCrossRefGoogle Scholar
  91. 91.
    Modak, S., and Cheung, N. K. (2007) Disialoganglioside directed immunotherapy of neuroblastoma, Cancer Invest., 25, 67–77.PubMedCrossRefGoogle Scholar
  92. 92.
    Gajdosik, Z. (2014) Racotumomab- a novel anti-idiotype monoclonal antibody vaccine for the treatment of cancer, Drugs Today (Barc.), 50, 301–307.CrossRefGoogle Scholar
  93. 93.
    Osorio, M., Gracia, E., Reigosa, E., Hernandez, J., de la Torre, A., Saurez, G., Perez, K., Viada, C., Cepeda, M., Carr, A., Avila, Y., Rodriguez, M., and Fernandez, L. E. (2012) Effect of vaccination with N-glycolyl GM3/VSSP vaccine by subcutaneous injection in patients with advanced cutaneous melanoma, Cancer Manag. Res., 4, 341–345.PubMedCentralPubMedCrossRefGoogle Scholar
  94. 94.
    Alfonso, S., Valdes-Zayas, A., Santiesteban, E. R., Flores, Y. I., Areces, F., Hernandez, M., Viada, C. E., Mendoza, I. C., Guerra, P. P., Garcia, E., Ortiz, R. A., de la Torre, A. V., Cepeda, M., Perez, K., Chong, E., Hernandez, A. M., Toledo, D., Gonzalez, Z., Mazorra, Z., Crombet, T, Perez, R., Vazquez, A. M., and Macias, A. E. (2014) A randomized, multicenter, placebo-controlled clinical trial of racotumomab-alum vaccine as switch maintenance therapy in advanced non-small cell lung cancer patients, Clin. Cancer Res., 20, 3660–3671.PubMedCrossRefGoogle Scholar
  95. 95.
    Kim, Y J., Choi, J. S., Seo, J., Song, J. Y, Lee, S. E., Kwon, M. J., Kwon, M. J., Kundu, J., Jung, K., Oh, E., Shin, Y K., and Choi, Y L. (2014) MET is a potential target for use in combination therapy with EGFR inhibition in triple-negative/basal-like breast cancer, Int. J. Cancer, 134, 2424–2436.PubMedCrossRefGoogle Scholar
  96. 96.
    Fu, P., Du, F., Yao, M., Lv, K., and Liu, Y. (2014) MicroRNA-185 inhibits proliferation by targeting c-Met in human breast cancer cells, Exp. Ther. Med., 8, 1879–1883.PubMedCentralPubMedGoogle Scholar
  97. 97.
    Dobrenkov, K., and Cheung, N. K. (2014) GD2-targeted immunotherapy and radioimmunotherapy, Semin. Oncol., 41, 589–612.PubMedCrossRefGoogle Scholar
  98. 98.
    Chames, P., and Baty, D. (2009) Bispecific antibodies for cancer therapy: the light at the end of the tunnel? MAbs, 1, 539–547.PubMedCentralPubMedCrossRefGoogle Scholar
  99. 99.
    Li, J., Liu, R., Yang, Y, Huang, Y, Li, X., Liu, R., and Shen, X. (2014) Triptolide-induced in vitro and in vivo cytotoxicity in human breast cancer stem cells and primary breast cancer cells, Oncol. Rep., 31, 2181–2186.PubMedGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2015

Authors and Affiliations

  1. 1.Structural and Functional Glycobiology Unit, UMR CNRS 8576University of LilleVilleneuve d’AscqFrance

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