Influence of Glycosylation on the Development and Treatment of Neuroblastoma
Main Article Content
Abstract
Neuroblastoma is a solid malignancy observed in pediatric patients developing when neuroblasts are unable to mature, leading to unregulated proliferation and tumor formation. Neuroblastoma is heterogeneous and aggressive in nature, leading to high treatment failure, morbidity, and mortality rates. Lewis family glycans, as part of the Core 2 O-glycans, play a key role in neuroblastoma malignant cell behavior in MYCN-amplified cell lines. Current treatment approaches for neuroblastoma include chemotherapy, surgery, and radiation. These approaches are faced with physiological and cellular barriers, including the less understood role of glycosylation in development and treatment. Studies have confirmed that the inhibition of mucin glycosylation has improved effectiveness of cytotoxic drug agents employed against solid malignancies such as with pancreatic cancer, yet little research is available regarding the influence of glycosylated proteins for other diseases. This article explores genetic defects associated with neuroblastoma such MYCN gene amplification at the time of diagnosis, as well as clinical approaches and therapeutic challenges encountered during treatment. Additionally, the article reviews experimental and clinical evidence in support of the influence of glycosylation in neuroblastoma development, and possible unfavorable impact of glycosylation on drug therapy.
Keywords:
Neuroblastoma, MYCN, Glycosylation, Mucin, pediatric cancer
Article Details
How to Cite
COOK, Meghan et al.
Influence of Glycosylation on the Development and Treatment of Neuroblastoma.
Medical Research Archives, [S.l.], v. 11, n. 6, june 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/3933>. Date accessed: 15 may 2024.
doi: https://doi.org/10.18103/mra.v11i6.3933.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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27. Uemura S, Ishida T, Thwin KKM, et al. Dynamics of Minimal Residual Disease in Neuroblastoma Patients. Front Oncol. 2019;9:455.
28. Angeli E, Nguyen TT, Janin A, Bousquet G. How to make anticancer drugs cross the blood-brain barrier to treat brain metastases. Int. J. Mol. 2020;21(1):22.
29. Bors LA, Erdo F. Overcoming the blood-brain barrier. challenges and tricks for CNS drug delivery. Sci. Pharm. 2019;87(1):6.
30. Yanagisawa T, Newman A, Coley H, Renshaw J, Pinkerton CR, Pritchard-Jones K. BIRICODAR (VX-710; Incel): an effective chemosensitizer in neuroblastoma. Br J Cancer. 1999;80(8):1190-1196.
31. Lin JW, Chen JT, Hong CY, et al. Honokiol transverses the blood-brain barrier and induces apoptosis of neuroblastoma cells via an intrinsic bax-mitochondion-cytochrome c-caspase protease pathway. Neuro Oncol. 2012;14(3):302-314.
32. Castellani C, Singer G, Eibisberger M, et al. The effects of neuroblastoma and chemotherapy on metabolism, fecal microbiome, volatile organic compounds, and gut barrier function in a murine model. Pediatr Res. 2019;85:546-555.
33. Tolbert VP, Matthay KK. Neuroblastoma: clinical and biological approach to risk stratification and treatment. Cell and tissue research. 2018;372(2):195-209.
34. Pearson AD, Pinkerton CR, Lewis IJ, Imeson J, Ellershaw C, Machin D. High-dose rapid and standard induction chemotherapy for patients aged over 1 year with stage 4 neuroblastoma: a randomised trial. The Lancet Oncology. 2008;9(3):247-256.
35. Berthold F, Boos J, Burdach S, et al. Myeloablative megatherapy with autologous stem-cell rescue versus oral maintenance chemotherapy as consolidation treatment in patients with high-risk neuroblastoma: a randomised controlled trial. The Lancet Oncology. 2005;6(9):649-658.
36. Hall MK, Weidner DA, Whitman AA, Schwalbe RA. Lack of complex type N-glycans lessens aberrant neuronal properties. PLoS One. 2018;13(6):e0199202.
37. Hall MK, Whitman AA, Weidner DA, Schwalbe RA. Knockdown of N-Acetylglucosaminyltransferase-II Reduces Matrix Metalloproteinase 2 Activity and Suppresses Tumorigenicity in Neuroblastoma Cell Line. Biology (Basel). 2020;9(4):71.
38. Del Grosso F, De Mariano M, Passoni L, Luksch R, Tonini GP, Longo L. Inhibition of N-linked glycosylation impairs ALK phosphorylation and disrupts pro-survival signaling in neuroblastoma cell lines. BMC Cancer. 2011;11:525.
39. Waechter CJ, Schmidt JW, Catterall WA. Glycosylation Is Required for Maintenance of Functional Sodium Channels in Neuroblastoma Cells. J Biol Chem. 1983;258(8):5117-5123.
40. Berois N, Blanc E, Ripoche H, et al. ppGalNAc-T13: A new molecular marker of bone marrow involvement in neuroblastoma. Clin. Chem. 2006;52(9):1701-1712.
41. Berois N, Osinaga E. Glycobiology of neuroblastoma: impact on tumor behavior, prognosis, and therapeutic strategies. Front Oncol. 2014;4:114.
42. Hsu WM, Che MI, Liao YF, et al. B4GALNT3 expression predicts a favorable prognosis and suppresses cell migration and invasion via β₁ integrin signaling in neuroblastoma. Am J Pathol. 2011;179(3):1394–1404.
43. Chang H-H, Chen C-H, Chou C-H, et al. β-1,4-Galactosyltransferase III Enhances Invasive Phenotypes Via β1-Integrin and Predicts Poor Prognosis in Neuroblastoma. Clinical Cancer Research. 2013;19(7):1705.
44. Alkholief M, Campbell RB. Investigating the role of mucin in the delivery of nanoparticles to cellular models of human cancer disease: An in vitro study. Nanomedicine : nanotechnology, biology, and medicine. 2016;12(5):1291-1302.
45. Song X, Airan RD, Arifin DR, et al. Label-free in vivo molecular imaging of underglycosylated mucin-1 expression in tumour cells. Nature Communications. 2015;6:6719.
46. Kalra AV, Campbell RB. Mucin overexpression limits the effectiveness of 5-FU by reducing intracellular drug uptake and antineoplastic drug effects in pancreatic tumours. Eur. J. Cancer. 2009;45(1):164-173.
47. Lefebvre T, Alonso C, Mahboub Sd, et al. Effect of okadaic acid on O-linked N-acetylglucosamine levels in a neuroblastoma cell line. Biochimica et Biophysica Acta (BBA) - General Subjects. 1999;1472(1):71-81.
48. Sieczkowski E, Lehner C, Ambros PF, Hohenegger M. Double impact on p-glycoprotein by statins enhances doxorubicin cytotoxicity in human neuroblastoma cells. International Journal of Cancer. 2010;126(9):2025-2035.
49. Natoni A, Farrell ML, Harris S, et al. Sialyltransferase inhibition leads to inhibition of tumor cell interactions with E-selectin, VCAM1, and MADCAM1, and improves survival in a human multiple myeloma mouse model. Haematologica. 2019:haematol.2018.212266.
50. Kalra AV, Campbell RB. Mucin impedes cytotoxic effect of 5-FU against growth of human pancreatic cancer cells: overcoming cellular barriers for therapeutic gain. Br J Cancer. 2007;97(7):910-918.
51. Wu J, Chen S, Liu H, et al. Tunicamycin specifically aggravates ER stress and overcomes chemoresistance in multidrug-resistant gastric cancer cells by inhibiting N-glycosylation. J Exp Clin Cancer Res. 2018;37(1):272.
52. 51. Lin MC, Chien PH, Wu HY, et al. C1GALT1 predicts poor prognosis and is a potential therapeutic target in head and neck cancer. Oncogene. 2018;37(43):5780-5793.
53. Lin NY, Chen ST, Chang HL, et al. C1GALT1 expression predicts a favorable prognosis and suppresses malignant phenotypes via TrkA signaling in neuroblastoma. Oncogenesis. 2022;11(1):8. Published 2022 Feb 15. doi:10.1038/s41389-022-00383-w
2. Neuroblastoma. St. Jude Children's Research Hospital. https://www.stjude.org/disease/neuroblastoma.html. Published 2019. Accessed June 11, 2019.
3. Ries LAG, Smith MA, Gurney JG, Linet M, Tamra T, Young JL, Bunin GR (eds). Cancer Incidence and Survival among Children and Adolescents: United States SEER Program 1975-1995, National Cancer Institute, SEER Program. NIH Pub. No. 99-4649. Bethesda, MD, 1999.
4. Neuroblastoma- Childhood: Signs and Symptoms. American Society of Clinical Oncology. https://www.cancer.net/cancer-types/neuroblastoma-childhood/symptoms-and-signs. Accessed October 27, 2020.
5. Neuroblastoma. Stanford Children’s Health. https://www.stanfordchildrens.org/en/topic/default?id=neuroblastoma-90-P02735. Published 2019. Accessed October 11, 2020.
6. Neuroblastoma Treatment. National Cancer Institute. https://www.cancer.gov/types/neuroblastoma/hp/neuroblastoma-treatment-pdq. Accessed June 12, 2019.
7. Allen-Rhoades W., Whittle S., Rainusso N. Pediatric solid tumors of infancy: an overview. Pediatr Rev. 2018;39(2):57-67.
8. Cuello H, Segatori V, ALbertó M, et al. Aberrant O-glycosylation modulates aggressiveness in neuroblastoma. Oncotarget. 2018;9(75):34176-88.
9. Ho WL, Hsu WM, Huang MC, Kadomatsu K, Nakagawara A. Protein Glycosylation in cancers and its potential therapeutic applications in neuroblastoma. J Hematol Oncol. 2016;9(1):100
10. Fotsis T, Breit S, Lutz W, et al. Down-regulation of endothelial cell growth inhibitors by enhanced MCYN oncogene expression in human neuroblastoma cells. Eur J Biochem. 1999;263:757-764.
11. Hatzi E, Murphy C, Zoephel A, et al. N-myc oncogene overexpression down-regulates leukemia inhibitory factor in neuroblastoma. Eur J Biochem. 2002;269(15):3732-3741.
12. Cheung NK, Zhang J, Parker M, et al. Association of age at diagnosis and genetic mutations in patients with neuroblastoma. JAMA. 2012:307(10):1062-1071.
13. Hasan MK, Nafady A, Takatori A, et al. ALK is a MYCN target gene and regulates cell migration and invasion in neuroblastoma. Sci Rep. 2013;3:3450.
14. De Mariano M, Gallesio R, Chierici M, et al. Identification of GALNT14 as a novel neuroblastoma predisposition gene. Oncotarget. 2015;6(28):26335-26346.
15. Lin WR, Yeh CT. GALNT14: an emerging marker capable of predicting therapeutic outcomes in multiple cancers. Int J Mol Sci. 2020;21(4):1491.
16. Gross N, Balmas K, Brognara CB. Absence of functional CD44 hyaluronan receptor on human NMYC-amplified neuroblastoma cells. Cancer Res. 1997;57(7):1387-1393.
17. Elzembely MM, Dahlberg AE, Pinto N, et al. Late effects in high‐risk neuroblastoma survivors treated with high‐dose chemotherapy and stem cell rescue. Pediatr Blood Cancer. 2019; 66(1):e27421.
18. Abou-Antoun TJ, Nazarian J, Ghanem A, Vukmanovic S, Sandler AD. Molecular and functional analysis of anchorage independent, treatment-evasive neuroblastoma tumorspheres with enhanced malignant properties: A possible explanation for radio-therapy resistance. PLoS One. 2018;13(1):e0189711.
19. Neuroblastoma in Children- In Treatment. https://curesearch.org/Neuroblastoma-In-Treatment. Accessed July 10, 2019.
20. Bocca P, Carlo ED, Emionite L, et al. Bevacizumab-mediated tumor vasculature remodeling improves tumor infiltration and antitumor efficacy of GD2-CAR T cells in a human neuroblastoma preclinical model. OncoImmunology. 2018;7(1).
21. Tarp MA, Clausen H. Mucin-type O-glycosylation and its potential use in drug and vaccine development. Biochimica et Biophysica Acta. 2008;1780(3):546-563.
22. Zeineldin M, Federico S, Chem X, et al. MYCN amplification and ATRX mutations are incompatible in neuroblastoma. Nat Commun. 2020:11(1):913.
23. Ho R, Eggert A, Hishiki T, et al. Resistance to chemotherapy mediated by TrkB in neuroblastomas. Cancer Res. 2002;62(22):6462-6466.
24. Schramm A, Schulte JH, Astrahantseff K, et al. Biological Effect of TrkA and TrkB receptor signaling in neuroblastoma. Cancer Lett. 2005;228(1-2):143-153.
25. De Moerloose B, Van de Wiele C, Dhooge C, et al. Technetium-99m sestamibi imaging in paediatric neuroblastoma and ganglioneuroma and its relation to P-glycoprotein. Eur J of Nucl Med. 1999;26(4):396.
26. Ferrandis E, Da Silva J, Riou G, Bénard I. Coactivation of the MDR1 and MYCN genes in human neuroblastoma cells during the metastatic process in the nude mouse. Cancer Res. 1994;54(8):2256-2261.
27. Uemura S, Ishida T, Thwin KKM, et al. Dynamics of Minimal Residual Disease in Neuroblastoma Patients. Front Oncol. 2019;9:455.
28. Angeli E, Nguyen TT, Janin A, Bousquet G. How to make anticancer drugs cross the blood-brain barrier to treat brain metastases. Int. J. Mol. 2020;21(1):22.
29. Bors LA, Erdo F. Overcoming the blood-brain barrier. challenges and tricks for CNS drug delivery. Sci. Pharm. 2019;87(1):6.
30. Yanagisawa T, Newman A, Coley H, Renshaw J, Pinkerton CR, Pritchard-Jones K. BIRICODAR (VX-710; Incel): an effective chemosensitizer in neuroblastoma. Br J Cancer. 1999;80(8):1190-1196.
31. Lin JW, Chen JT, Hong CY, et al. Honokiol transverses the blood-brain barrier and induces apoptosis of neuroblastoma cells via an intrinsic bax-mitochondion-cytochrome c-caspase protease pathway. Neuro Oncol. 2012;14(3):302-314.
32. Castellani C, Singer G, Eibisberger M, et al. The effects of neuroblastoma and chemotherapy on metabolism, fecal microbiome, volatile organic compounds, and gut barrier function in a murine model. Pediatr Res. 2019;85:546-555.
33. Tolbert VP, Matthay KK. Neuroblastoma: clinical and biological approach to risk stratification and treatment. Cell and tissue research. 2018;372(2):195-209.
34. Pearson AD, Pinkerton CR, Lewis IJ, Imeson J, Ellershaw C, Machin D. High-dose rapid and standard induction chemotherapy for patients aged over 1 year with stage 4 neuroblastoma: a randomised trial. The Lancet Oncology. 2008;9(3):247-256.
35. Berthold F, Boos J, Burdach S, et al. Myeloablative megatherapy with autologous stem-cell rescue versus oral maintenance chemotherapy as consolidation treatment in patients with high-risk neuroblastoma: a randomised controlled trial. The Lancet Oncology. 2005;6(9):649-658.
36. Hall MK, Weidner DA, Whitman AA, Schwalbe RA. Lack of complex type N-glycans lessens aberrant neuronal properties. PLoS One. 2018;13(6):e0199202.
37. Hall MK, Whitman AA, Weidner DA, Schwalbe RA. Knockdown of N-Acetylglucosaminyltransferase-II Reduces Matrix Metalloproteinase 2 Activity and Suppresses Tumorigenicity in Neuroblastoma Cell Line. Biology (Basel). 2020;9(4):71.
38. Del Grosso F, De Mariano M, Passoni L, Luksch R, Tonini GP, Longo L. Inhibition of N-linked glycosylation impairs ALK phosphorylation and disrupts pro-survival signaling in neuroblastoma cell lines. BMC Cancer. 2011;11:525.
39. Waechter CJ, Schmidt JW, Catterall WA. Glycosylation Is Required for Maintenance of Functional Sodium Channels in Neuroblastoma Cells. J Biol Chem. 1983;258(8):5117-5123.
40. Berois N, Blanc E, Ripoche H, et al. ppGalNAc-T13: A new molecular marker of bone marrow involvement in neuroblastoma. Clin. Chem. 2006;52(9):1701-1712.
41. Berois N, Osinaga E. Glycobiology of neuroblastoma: impact on tumor behavior, prognosis, and therapeutic strategies. Front Oncol. 2014;4:114.
42. Hsu WM, Che MI, Liao YF, et al. B4GALNT3 expression predicts a favorable prognosis and suppresses cell migration and invasion via β₁ integrin signaling in neuroblastoma. Am J Pathol. 2011;179(3):1394–1404.
43. Chang H-H, Chen C-H, Chou C-H, et al. β-1,4-Galactosyltransferase III Enhances Invasive Phenotypes Via β1-Integrin and Predicts Poor Prognosis in Neuroblastoma. Clinical Cancer Research. 2013;19(7):1705.
44. Alkholief M, Campbell RB. Investigating the role of mucin in the delivery of nanoparticles to cellular models of human cancer disease: An in vitro study. Nanomedicine : nanotechnology, biology, and medicine. 2016;12(5):1291-1302.
45. Song X, Airan RD, Arifin DR, et al. Label-free in vivo molecular imaging of underglycosylated mucin-1 expression in tumour cells. Nature Communications. 2015;6:6719.
46. Kalra AV, Campbell RB. Mucin overexpression limits the effectiveness of 5-FU by reducing intracellular drug uptake and antineoplastic drug effects in pancreatic tumours. Eur. J. Cancer. 2009;45(1):164-173.
47. Lefebvre T, Alonso C, Mahboub Sd, et al. Effect of okadaic acid on O-linked N-acetylglucosamine levels in a neuroblastoma cell line. Biochimica et Biophysica Acta (BBA) - General Subjects. 1999;1472(1):71-81.
48. Sieczkowski E, Lehner C, Ambros PF, Hohenegger M. Double impact on p-glycoprotein by statins enhances doxorubicin cytotoxicity in human neuroblastoma cells. International Journal of Cancer. 2010;126(9):2025-2035.
49. Natoni A, Farrell ML, Harris S, et al. Sialyltransferase inhibition leads to inhibition of tumor cell interactions with E-selectin, VCAM1, and MADCAM1, and improves survival in a human multiple myeloma mouse model. Haematologica. 2019:haematol.2018.212266.
50. Kalra AV, Campbell RB. Mucin impedes cytotoxic effect of 5-FU against growth of human pancreatic cancer cells: overcoming cellular barriers for therapeutic gain. Br J Cancer. 2007;97(7):910-918.
51. Wu J, Chen S, Liu H, et al. Tunicamycin specifically aggravates ER stress and overcomes chemoresistance in multidrug-resistant gastric cancer cells by inhibiting N-glycosylation. J Exp Clin Cancer Res. 2018;37(1):272.
52. 51. Lin MC, Chien PH, Wu HY, et al. C1GALT1 predicts poor prognosis and is a potential therapeutic target in head and neck cancer. Oncogene. 2018;37(43):5780-5793.
53. Lin NY, Chen ST, Chang HL, et al. C1GALT1 expression predicts a favorable prognosis and suppresses malignant phenotypes via TrkA signaling in neuroblastoma. Oncogenesis. 2022;11(1):8. Published 2022 Feb 15. doi:10.1038/s41389-022-00383-w