Journal of Korean Neurosurgical Society

The Korean Neurosurgical Society (대한신경외과학회)
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Nerve Growth Factor Stimulates Glioblastoma Proliferation through Notch1 Receptor Signaling

  • Park, Jun Chul (Department of Neurosurgery, Hallym University Sacred Heart Hospital) ;
  • Chang, In Bok (Department of Neurosurgery, Hallym University Sacred Heart Hospital) ;
  • Ahn, Jun Hyong (Department of Neurosurgery, Hallym University Sacred Heart Hospital) ;
  • Kim, Ji Hee (Department of Neurosurgery, Hallym University Sacred Heart Hospital) ;
  • Song, Joon Ho (Department of Neurosurgery, Hallym University Sacred Heart Hospital) ;
  • Moon, Seung Myung (Department of Neurosurgery, Dongtan Sacred Heart Hospital) ;
  • Park, Young-Han (Department of Obstetrics and Gynecology, Hallym University Sacred Heart Hospital)
  • Received : 2017.07.24
  • Accepted : 2018.01.09
  • Published : 2018.07.01
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Abstract

Objective : Notch receptors are heterodimeric transmembrane proteins that regulate cell fate, such as differentiation, proliferation, and apoptosis. Dysregulated Notch pathway signaling has been observed in glioblastomas, as well as in other human malignancies. Nerve growth factor (NGF) is essential for cell growth and differentiation in the nervous system. Recent reports suggest that NGF stimulates glioblastoma proliferation. However, the relationship between NGF and Notch1 in glioblastomas remains unknown. Therefore, we investigated expression of Notch1 in a glioblastoma cell line (U87-MG), and examined the relationship between NGF and Notch1 signaling. Methods : We evaluated expression of Notch1 in human glioblastomas and normal brain tissues by immunohistochemical staining. The effect of NGF on glioblastoma cell line (U87-MG) was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. To evaluate the relationship between NGF and Notch1 signaling, Notch1 and Hes1 expression were evaluated by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. To confirm the effects of NGF on Notch1 signaling, Notch1 and Hes1 small interfering RNAs (siRNAs) were used. Results : In immunohistochemistry, Notch1 expression was higher in glioblastoma than in normal brain tissue. MTT assay showed that NGF stimulates U87-MG cells in a dose-dependent manner. RT-PCR and Western blot analysis demonstrated that Notch1 and Hes1 expression were increased by NGF in a dose-dependent manner. After transfection with Notch1 and Hes1 siRNAs, there was no significant difference between controls and 100 nM $NGF-{\beta}$, which means that U87-MG cell proliferation was suppressed by Notch1 and Hes1 siRNAs. Conclusion : These results indicate that NGF stimulates glioblastoma cell proliferation via Notch1 signaling through Hes 1.

Keywords

References

  1. Artavanis-Tsakonas S, Rand MD, Lake RJ : Notch signaling: cell fate control and signal integration in development. Science 284 : 770-776, 1999 https://doi.org/10.1126/science.284.5415.770
  2. Aster JC, Pear WS : Notch signaling in leukemia. Curr Opin Hematol 8 : 237-244, 2001 https://doi.org/10.1097/00062752-200107000-00010
  3. Bigas A, Martin DI, Milner LA : Notch1 and Notch2 inhibit myeloid differentiation in response to different cytokines. Mol Cell Biol 18 : 2324- 2333, 1998 https://doi.org/10.1128/MCB.18.4.2324
  4. Bolós V, Grego-Bessa J, de la Pompa JL : Notch signaling in development and cancer. Endocr Rev 28 : 339-363, 2007 https://doi.org/10.1210/er.2006-0046
  5. Brown MC, Staniszewska I, Lazarovici P, Tuszynski GP, Del Valle L, Marcinkiewicz C : Regulatory effect of nerve growth factor in alpha9beta1 integrin-dependent progression of glioblastoma. Neuro Oncol 10 : 968-980, 2008 https://doi.org/10.1215/15228517-2008-0047
  6. Chao MV, Hempstead BL : p75 and Trk: a two-receptor system. Trends Neurosci 18 : 321-326, 1995 https://doi.org/10.1016/0166-2236(95)93922-K
  7. Chen J, Kesari S, Rooney C, Strack PR, Chen J, Shen H, et al. : Inhibition of Notch signaling blocks growth of glioblastoma cell lines and tumor neurospheres. Genes Cancer 1 : 822-835, 2010 https://doi.org/10.1177/1947601910383564
  8. Cheung HC, Corley LJ, Fuller GN, McCutcheon IE, Cote GJ : Polypyrimidine tract binding protein and notch1 are independently re-expressed in glioma. Mod Pathol 19 : 1034-1041, 2006 https://doi.org/10.1038/modpathol.3800635
  9. Faux CH, Turnley AM, Epa R, Cappai R, Bartlett PF : Interactions between fibroblast growth factors and notch regulate neuronal differentiation. J Neurosci 21 : 5587-5596, 2001 https://doi.org/10.1523/JNEUROSCI.21-15-05587.2001
  10. Giraud S, Loum E, Bessette B, Mathonnet M, Lalloue F : P75 neurotrophin receptor is sequestered in the Golgi apparatus of the U-87 MG human glioblastoma cell line. Int J Oncol 38 : 391-399, 2011
  11. Goretzki PE, Wahl RA, Becker R, Koller C, Branscheid D, Grussendorf M, et al. : Nerve growth factor (NGF) sensitizes human medullary thyroid carcinoma (hMTC) cells for cytostatic therapy in vitro. Surgery 102 : 1035-1042, 1987
  12. Greenwald I : LIN-12/Notch signaling: lessons from worms and flies. Genes Dev 12 : 1751-1762, 1998 https://doi.org/10.1101/gad.12.12.1751
  13. Jang MS, Zlobin A, Kast WM, Miele L : Notch signaling as a target in multimodality cancer therapy. Curr Opin Mol Ther 2 : 55-65, 2000
  14. Jian Q, Tao Z, Li Y, Yin ZQ : Acute retinal injury and the relationship between nerve growth factor, notch1 transcription and short-lived dedifferentiation transient changes of mammalian Müller cells. Vision Res 110(Pt A) : 107-117, 2015 https://doi.org/10.1016/j.visres.2015.01.030
  15. Jundt F, Anagnostopoulos I, Förster R, Mathas S, Stein H, Dorken B : Activated Notch1 signaling promotes tumor cell proliferation and survival in Hodgkin and anaplastic large cell lymphoma. Blood 99 : 3398-3403, 2002 https://doi.org/10.1182/blood.V99.9.3398
  16. Kanu OO, Mehta A, Di C, Lin N, Bortoff K, Bigner DD, et al. : Glioblastoma multiforme: a review of therapeutic targets. Expert Opin Ther Targets 13 : 701-718, 2009 https://doi.org/10.1517/14728220902942348
  17. Kopan R, Ilagan MX : The canonical notch signaling pathway: unfolding the activation mechanism. Cell 137 : 216-233, 2009 https://doi.org/10.1016/j.cell.2009.03.045
  18. Lawn S, Krishna N, Pisklakova A, Qu X, Fenstermacher DA, Fournier M, et al. : Neurotrophin signaling via TrkB and TrkC receptors promotes the growth of brain tumor-initiating cells. J Biol Chem 290 : 3814-3824, 2015 https://doi.org/10.1074/jbc.M114.599373
  19. Leong KG, Karsan A : Recent insights into the role of Notch signaling in tumorigenesis. Blood 107 : 2223-2233, 2006 https://doi.org/10.1182/blood-2005-08-3329
  20. Li J, Cui Y, Gao G, Zhao Z, Zhang H, Wang X : Notch1 is an independent prognostic factor for patients with glioma. J Surg Oncol 103 : 813-817, 2011 https://doi.org/10.1002/jso.21851
  21. Liu Y, Su C, Shan Y, Yang S, Ma G : Targeting notch1 inhibits invasion and angiogenesis of human breast cancer cells via inhibition nuclear factor- kappaB signaling. Am J Transl Res 8 : 2681-2692, eCollection 2016
  22. Miele L, Golde T, Osborne B : Notch signaling in cancer. Curr Mol Med 6 : 905-918, 2006 https://doi.org/10.2174/156652406779010830
  23. Miele L, Miao H, Nickoloff BJ : Notch signaling as a novel cancer therapeutic target. Curr Cancer Drug Targets 6 : 313-323, 2006 https://doi.org/10.2174/156800906777441771
  24. Nicolas M, Wolfer A, Raj K, Kummer JA, Mill P, van Noort M, et al. : Notch1 functions as a tumor suppressor in mouse skin. Nat Genet 33 : 416-421, 2003 https://doi.org/10.1038/ng1099
  25. Oelmann E, Sreter L, Schuller I, Serve H, Koenigsmann M, Wiedenmann B, et al. : Nerve growth factor stimulates clonal growth of human lung can- cer cell lines and a human glioblastoma cell line expressing high-affinity nerve growth factor binding sites involving tyrosine kinase signaling. Cancer Res 55 : 2212-2219, 1995
  26. Park YH, Kim SJ, Jeong BH, Herzog TJ, Wright J, Kitajewski J, et al. : Follicular stimulating hormone enhances Notch 1 expression in SK-OV-3 ovarian cancer cells. J Gynecol Oncol 21 : 119-124, 2010 https://doi.org/10.3802/jgo.2010.21.2.119
  27. Phillips HS, Kharbanda S, Chen R, Forrest WF, Soriano RH, Wu TD, et al. : Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 9 : 157-173, 2006 https://doi.org/10.1016/j.ccr.2006.02.019
  28. Purow BW, Haque RM, Noel MW, Su Q, Burdick MJ, Lee J, et al. : Expres- sion of Notch-1 and its ligands, Delta-like-1 and Jagged-1, is critical for glioma cell survival and proliferation. Cancer Res 65 : 2353-2363, 2005 https://doi.org/10.1158/0008-5472.CAN-04-1890
  29. Qian XQ, Chen LL, Cheng Q, Tian Y, Luo XF, Wan XY : Inhibition of Notch 1 receptor influenced the differentiation of Lin-CD45RA-dendritic cell precursors within ovarian carcinoma microenvironment. BMC Immunol 17 : 14, 2016 https://doi.org/10.1186/s12865-016-0150-3
  30. Rakowicz-Szulczyńska EM, Herlyn M, Koprowski H : Nerve growth factor receptors in chromatin of melanoma cells, proliferating melanocytes, and colorectal carcinoma cells in vitro. Cancer Res 48(24 Pt 1) : 7200-7206, 1988
  31. Rakowicz-Szulczynska EM, Reddy U, Vorbrodt A, Herlyn D, Koprowski H : Chromatin and cell surface receptors mediate melanoma cell growth response to nerve growth factor. Mol Carcinog 4 : 388-396, 1991 https://doi.org/10.1002/mc.2940040511
  32. Revoltella RP, Butler RH : Nerve growth factor may stimulate either division or differentiation of cloned C1300 neuroblastoma cells in serumfree cultures. J Cell Physiol 104 : 27-33, 1980 https://doi.org/10.1002/jcp.1041040105
  33. Singer HS, Hansen B, Martinie D, Karp CL : Mitogenesis in glioblastoma multiforme cell lines: a role for NGF and its TrkA receptors. J Neurooncol 45 : 1-8, 1999 https://doi.org/10.1023/A:1006323523437
  34. Sofroniew MV, Howe CL, Mobley WC : Nerve growth factor signaling, neuroprotection, and neural repair. Annu Rev Neurosci 24 : 1217-1281, 2001 https://doi.org/10.1146/annurev.neuro.24.1.1217
  35. Sriuranpong V, Borges MW, Ravi RK, Arnold DR, Nelkin BD, Baylin SB, et al. : Notch signaling induces cell cycle arrest in small cell lung cancer cells. Cancer Res 61 : 3200-3205, 2001
  36. Ström A, Castella P, Rockwood J, Wagner J, Caudy M : Mediation of NGF signaling by post-translational inhibition of HES-1, a basic helix-loop- helix repressor of neuronal differentiation. Genes Dev 11 : 3168-3181, 1997 https://doi.org/10.1101/gad.11.23.3168
  37. Takei Y, Laskey R : Interpreting crosstalk between TNF-alpha and NGF: po- tential implications for disease. Trends Mol Med 14 : 381-388, 2008 https://doi.org/10.1016/j.molmed.2008.07.002
  38. Xu P, Yu S, Jiang R, Kang C, Wang G, Jiang H, et al. : Differential expres- sion of Notch family members in astrocytomas and medulloblastomas. Pathol Oncol Res 15 : 703-710, 2009 https://doi.org/10.1007/s12253-009-9173-x
  39. Yavropoulou MP, Maladaki A, Yovos JG : The role of Notch and Hedge- hog signaling pathways in pituitary development and pathogenesis of pituitary adenomas. Hormones (Athens) 14 : 5-18, 2015 https://doi.org/10.1007/BF03401377
  40. Zlobin A, Jang M, Miele L : Toward the rational design of cell fate modi- fiers: Notch signaling as a target for novel biopharmaceuticals. Curr Pharm Biotechnol 1 : 83-106, 2000 https://doi.org/10.2174/1389201003379013

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