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Ganglioside as a Therapy Target in Various Types of Cancer

  • Qamsari, Elmira Safaie (Department of Immunology, Tabriz University of Medical Sciences) ;
  • Nourazarian, Alireza (Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences) ;
  • Bagheri, Salman (Department of Immunology, Tabriz University of Medical Sciences) ;
  • Motallebnezhad, Morteza (Department of Immunology, Tabriz University of Medical Sciences)
  • Published : 2016.06.01

Abstract

Since their discovery in 1940, it has been well established that gangliosides are associated with a number of biological pathways and cellular processes such as growth, differentiation and toxin uptake. Gangliosides are glycosphingolipids containing neuraminic acid which are expressed on the plasma membrane of cells particularly in the nervous system. Heterogeneity and structural variation in the carbohydrate chains of gangliosides contributes to unique features of each of these molecules. Thirty five years ago it was discovered that aberrant glycosylation occurs in a variety of human cancers, including aberrant glycosylation of gangliosides. Ganglioside expression in terms of quality and quantity varies in different cancers and different roles may be played. Gangliosides, by affecting the immune system, including esxpression of cytokines and adhesion molecules, may inhibit anti-tumor mechanisms, as well as having direct impact on angiogenesis, cell movement and metastasis. It should be noted that different kinds of gangliosides do not all act by the same mechanisms.

Keywords

Gangliosides;cancer;immune system;biological pathways

References

  1. Battula VL, Shi Y, Evans KW, et al (2012). Ganglioside GD2 identifies breast cancer stem cells and promotes tumorigenesis. J Clin Invest, 122, 2066-78. https://doi.org/10.1172/JCI59735
  2. Bharti AC, Singh SM (2001). Gangliosides derived from a T cell lymphoma inhibit bone marrow cell proliferation and differentiation. Int. Immunopharmacol, 1, 155-165. https://doi.org/10.1016/S1567-5769(00)00004-7
  3. Birkle S, Zeng G, Gao L, Yu RK, Aubry J (2003). Role of tumorassociated gangliosides in cancer progression. Biochimie, 85, 455-63. https://doi.org/10.1016/S0300-9084(03)00006-3
  4. Biswas K, Richmond A, Rayman P, et al (2006). GM2 expression in renal cell carcinoma: potential role in tumor-induced T-cell dysfunction. Cancer Res, 66, 6816-25. https://doi.org/10.1158/0008-5472.CAN-06-0250
  5. Boligan KF, Mesa C, Fernandez LE, von Gunten S (2015). Cancer intelligence acquired (CIA): tumor glycosylation and sialylation codes dismantling antitumor defense. Cell Mol Life Sci, 72, 1231-48. https://doi.org/10.1007/s00018-014-1799-5
  6. Bull C, den Brok MH, Adema GJ (2014). Sweet escape: sialic acids in tumor immune evasion. Biochim Biophys Acta, 1846, 238-46.
  7. Caldwel S, Heitger A, Shen W, et al (2003) Mechanisms of ganglioside inhibition of APC function. J Immunol, 171, 1676-83. https://doi.org/10.4049/jimmunol.171.4.1676
  8. Cui XB, Peng H, Li S, et al (2014). Prognostic value of PLCE1 expression in upper gastrointestinal cancer: a systematic review and meta-analysis. Asian Pac J Cancer Prev, 15, 9661-6. https://doi.org/10.7314/APJCP.2014.15.22.9661
  9. Doronin II, Vishnyakova PA, Ponomarev ED, et al (2014). Ganglioside GD2 in reception and transduction of cell death signal in tumor cells. BMC Cancer, 14, 295. https://doi.org/10.1186/1471-2407-14-295
  10. Dyatlovitskaya EV, Kandyba AG (2006). Sphingolipids in tumor metastases and angiogenesis. Biochemistry (Moscow), 71, 347-53. https://doi.org/10.1134/S0006297906040018
  11. Elgert KD, Alleva DG, Mullins DW (1998). Tumor-induced immune dysfunction: the macrophage connection. J Leukoc Biol, 64, 275-90. https://doi.org/10.1002/jlb.64.3.275
  12. Fernandez LE, Gabri MR, Guthmann MD, et al (2010). NGcGM3 ganglioside: a privileged target for cancer vaccines. Clin Dev Immunol, 8 ,1-8.
  13. Fukumoto S, Mutoh T, Hasegawa T (2000). GD3 synthase gene expression in PC12 cells results in the continuous activation of TrkA and ERK1/2 and enhanced proliferation. J Biol Chem. 275, 5832-8. https://doi.org/10.1074/jbc.275.8.5832
  14. Garcia-Ruiz C, Morales A, Fernandez-Checa JC (2015). Glycosphingolipids and cell death: one aim, many ways. Apoptosis, 20, 607-20. https://doi.org/10.1007/s10495-015-1092-6
  15. Gately S (2000). The contributions of cyclooxygenase-2 to tumor angiogenesis. Cancer Metastasis Rev, 19, 19-27. https://doi.org/10.1023/A:1026575610124
  16. Gu Y, Zhang J, Mi W (2008). Silencing of GM3 synthase suppresses lung metastasis of murine breast cancer cells. Breast Cancer Res, 10, 1.
  17. Hakomori S (2002). Glycosylation defining cancer malignancy: new wine in an old bottle. Proc Natl Acad Sci U S A. 99, 10231-3. https://doi.org/10.1073/pnas.172380699
  18. Hata K, Tochigi T, Sato I, et al (2015). Increased sialidase activity in serum of cancer patients: Identification of sialidase and inhibitor activities in human serum. Cancer Sci, 106, 383-9. https://doi.org/10.1111/cas.12627
  19. Holst S, Stavenhagen K, Balog CI, et al (2013) . Investigations on aberrant glycosylation of glycosphingolipids in colorectal cancer tissues using liquid chromatography and matrixassisted laser desorption time-of-flight mass spectrometry (MALDI-TOF-MS). Mol Cell Proteomics, 12, 3081-93. https://doi.org/10.1074/mcp.M113.030387
  20. Horwacik I, Rokita H (2015). Targeting of tumor-associated gangliosides with antibodies affects signaling pathways and leads to cell death including apoptosis. Apoptosis, 20, 679-88. https://doi.org/10.1007/s10495-015-1103-7
  21. Kakugawa Y, Wada T, Yamaguchi K, et al (2002). Up-regulation of plasma membrane-associated ganglioside sialidase (Neu3) in human colon cancer and its involvement in apoptosis suppression. Natl Acad Sci U S A, 99, 10718-23. https://doi.org/10.1073/pnas.152597199
  22. Krengel U, Bousquet PA (2014). Molecular recognition of gangliosides and their potential for cancer immunotherapies. Front Immunol, 21, 325.
  23. Kwak DH, Seo BB, Chang KT, Choo YK (2011). Roles of gangliosides in mouse embryogenesis and embryonic stem cell differentiation. Exp Mol Med, 43, 379-388. https://doi.org/10.3858/emm.2011.43.7.048
  24. Labrada M, Clavell M, Bebelagua Y (2010). Direct validation of NGcGM3 ganglioside as a new target for cancer immunotherapy. Expert Opin Biol Ther, 10, 153-62. https://doi.org/10.1517/14712590903443084
  25. Li Y, Huang X, Zhong W, Zhang J, Ma K (2013). Ganglioside GM3 promotes HGF-stimulatedmotility of murine hepatoma cell through enhanced phosphorylation of cMet at specific tyrosine sites and PI3K/Akt-mediated migration signaling, Mol Cell Biochem, 382, 83-92. https://doi.org/10.1007/s11010-013-1720-9
  26. Liu Y, Wondimu A, Yan S, Bobb D, Ladisch S (2014). Tumor gangliosides accelerate murine tumor angiogenesis. Angiogenesis, 17, 563-71. https://doi.org/10.1007/s10456-013-9403-4
  27. Mehrabani D, Shamsdin SA, Dehghan A, Safarpour A (2014). Clinical significance of serum vascular endothelial growth factor and complement 3a levels in patients with colorectal cancer in southern Iran. Asian Pac J Cancer Prev, 15, 9713-7. https://doi.org/10.7314/APJCP.2014.15.22.9713
  28. Miyagi T, Takahashi K, Shiozaki K, Yamaguchi K, Hosono M (2015). Plasma membrane-associated sialidase confers cancer initiation, promotion and progression. Adv Exp Med Biol, 842, 139-45. https://doi.org/10.1007/978-3-319-11280-0_9
  29. Mousavi SM,Ramazani R,Gouya MM, et al (2009). Cancer incidence and mortality in Iran. Ann Oncol. 20, 556-563.
  30. Niethammer D, Handgretinger R (1995). Clinical strategies for the treatment of neuroblastoma. Eur J Cancer. 31, 568-71. https://doi.org/10.1016/0959-8049(95)00032-E
  31. Nourazarian AR, Kangari P Salmaninejad A (2014). Roles of oxidative stress in the development and progression of breast cancer. Asian Pac J Cancer Prev, 15, 4745-51. https://doi.org/10.7314/APJCP.2014.15.12.4745
  32. Reis CA, Osorio H, Silva L, Gomes C, David L (2010). Alterations in glycosylation as biomarkers for cancer detection. J Clin Pathol, 63, 322-9. https://doi.org/10.1136/jcp.2009.071035
  33. Shurin GV, Shurin MR, Bykovskaia S, et al (2001). Neuroblastoma-derived gangliosides inhibit dendritic cell generation and function. Cancer Res, 61, 363-9.
  34. Steelant WF, Kawakami Y, Ito A, et al (2002). Monosialyl-Gb5 organized with cSrc and FAK in GEM of human breast carcinoma MCF-7 cells defines their invasive properties. FEBS letters, 531, 93-8. https://doi.org/10.1016/S0014-5793(02)03484-1
  35. Steiner T, Junker U, Henzgen B, et al (2001). Interferon-alpha suppresses the antiapoptotic effect of NF-kB and sensitizes renal cell carcinoma cells in vitro to chemotherapeutic drugs. Eur Urol, 39, 478-83. https://doi.org/10.1159/000052489
  36. Tringali C, Silvestri I, Testa F, et al (2014). Molecular subtyping of metastatic melanoma based on cell ganglioside metabolism profiles. BMC Cancer, 14, 560. https://doi.org/10.1186/1471-2407-14-560
  37. Wang Y, Cui Y, Cao F, et al (2015). Ganglioside GD1a suppresses LPS-induced pro-inflammatory cytokines in RAW264.7 macrophages by reducing MAPKs and NF-${\kappa}B$ signaling pathways through TLR4. Int Immunopharmacol, 28, 136-45. https://doi.org/10.1016/j.intimp.2015.05.044
  38. Wang Z, Ma L, Zhang XM, Zhou ZX (2014). Risk of lymph node metastases from early gastric cancer in relation to depth of invasion: experience in a single institution. Asian Pac J Cancer Prev, 15, 5371-5. https://doi.org/10.7314/APJCP.2014.15.13.5371
  39. Zamfir AD, Serb A, Vukeli Z, et al (2011). Assessment of the molecular expression and structure of gangliosides in brain metastasis of lung adenocarcinoma by an advanced approach based on fully automated chip-nanoelectrospray mass spectrometry. J Am Soc Mass Spectrom, 22, 2145-59. https://doi.org/10.1007/s13361-011-0250-5
  40. Zeng G, Gao L, Birkle S, Yu RK (2000). Suppression of ganglioside GD3 expression in a rat F-11 tumor cell line reduces tumor growth, angiogenesis, and vascular endothelial growth factor production, Cancer Res, 60, 6670-7.