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Mouse Nerve Growth Factor Facilitates the Growth of Interspinal Schwannoma Cells by Activating NGF Receptors

  • Liu, Shu Yi (School of Clinical Medicine, Xi'an Medical University) ;
  • Liu, Sheng Ze (Department of Neurosurgery, Fuzhou Second Affiliated Hospital of Xiamen University) ;
  • Li, Yu (Department of Otolaryngology, Second Affiliated Hospital of Xi'an Medical University) ;
  • Chen, Shi (Department of Neurosurgery, Fuzhou Second Affiliated Hospital of Xiamen University)
  • Received : 2019.03.27
  • Accepted : 2019.05.23
  • Published : 2019.11.01

Abstract

Objective : Nerve growth factor (NGF) is a member of the neurotrophic factor family and plays a vital role in the physiological processes of organisms, especially in the nervous system. Many recent studies have reported that NGF is also involved in the regulation of tumourigenesis by either promoting or suppressing tumor growth, which depends on the location and type of tumor. However, little is known regarding the effect of NGF on interspinal schwannoma (IS). In the present study, we aimed to explored whether mouse nerve growth factor (mNGF), which is widely used in the clinic, can influence the growth of interspinal schwannoma cells (ISCs) isolated from IS in vitro. Methods : ISCs were isolated, cultured and identified by S-100 with immunofluorescence analysis. S-100-positive cells were divided into five groups, and separately cultured with various concentrations of mNGF (0 [phosphate buffered saline, PBS], 40, 80, 160, and 320 ng/mL) for 24 hours. Western blot and quantantive real time polymerase chain reaction (PCR) were applied to detect tyrosine kinase A (TrkA) receptor and p75 neurotrophin receptor ($p75^{NTR}$) in each group. Crystal violet staining was selected to assess the effect of mNGF (160 ng/mL) on ISCs growth. Results : ISCs growth was enhanced by mNGF in a dose-dependent manner. The result of crystal violet staining revealed that it was significantly strengthened the cells growth kinetics when cultured with 160 ng/mL mNGF compared to PBS group. Western blot and quantantive real time PCR discovered that TrkA receptor and mRNA expression were both up-regualated under the condition of mNGF, expecially in 160 ng/mL, while the exoression of $p75^{NTR}$ demonstrated no difference among groups. Conclusion : From these data, we conclude that exogenous mNGF can facilitate ISC growth by activating both TrkA receptor and $p75^{NTR}$. In addition, patients who are suffering from IS should not be administered mNGF in the clinic.

Keywords

References

  1. Ahmad I, Yue WY, Fernando A, Clark JJ, Woodson EA, Hansen MR : p75NTR is highly expressed in vestibular schwannomas and promotes cell survival by activating nuclear transcription factor kappa B. Glia 62 : 1699-1712, 2014 https://doi.org/10.1002/glia.22709
  2. Chattopadhyay S, Shubayev VI : MMP-9 controls Schwann cell proliferation and phenotypic remodeling via IGF-1 and ErbB receptor-mediated activation of MEK/ERK pathway. Glia 57 : 1316-1325, 2009 https://doi.org/10.1002/glia.20851
  3. Chou TT, Trojanowski JQ, Lee VM : A novel apoptotic pathway induced by nerve growth factor-mediated TrkA activation in medulloblastoma. J Biol Chem 275 : 565-570, 2000 https://doi.org/10.1074/jbc.275.1.565
  4. Davidson B, Reich R, Lazarovici P, Nesland JM, Skrede M, Risberg B, et al. : Expression and activation of the nerve growth factor receptor TrkA in serous ovarian carcinoma. Clin Cancer Res 9 : 2248-2259, 2003
  5. Friedman WJ : Proneurotrophins, seizures, and neuronal apoptosis. Neuroscientist 16 : 244-252, 2010 https://doi.org/10.1177/1073858409349903
  6. George DJ, Suzuki H, Bova GS, Isaacs JT : Mutational analysis of the TrkA gene in prostate cancer. Prostate 36 : 172-180, 1998 https://doi.org/10.1002/(SICI)1097-0045(19980801)36:3<172::AID-PROS5>3.0.CO;2-J
  7. Gu R, Liu JB, Zhang Q, Liu GY, Zhu QS : MRI diagnosis of intradural extramedullary tumors. J Cancer Res Ther 10 : 927-931, 2014 https://doi.org/10.4103/0973-1482.137993
  8. Haase G, Pettmann B, Raoul C, Henderson CE : Signaling by death receptors in the nervous system. Curr Opin Neurobiol 18 : 284-291, 2008 https://doi.org/10.1016/j.conb.2008.07.013
  9. Hellebrand EE, Varbiro G : Development of mitochondrial permeability transition inhibitory agents: a novel drug target. Drug Discov Ther 4 : 54-61, 2010
  10. Hondermarck H : Neurotrophins and their receptors in breast cancer. Cytokine Growth Factor Rev 23 : 357-365, 2012 https://doi.org/10.1016/j.cytogfr.2012.06.004
  11. Jeon JH, Hwang HS, Jeong JH, Park SH, Moon JG, Kim CH : Spinal schwannoma; analysis of 40 cases. J Korean Neurosurg Soc 43 : 135-138, 2008 https://doi.org/10.3340/jkns.2008.43.3.135
  12. Johnson TV, Bull ND, Martin KR : Neurotrophic factor delivery as a protective treatment for glaucoma. Exp Eye Res 93 : 196-203, 2011 https://doi.org/10.1016/j.exer.2010.05.016
  13. Khwaja F, Tabassum A, Allen J, Djakiew D : The p75(NTR) tumor suppressor induces cell cycle arrest facilitating caspase mediated apoptosis in prostate tumor cells. Biochem Biophys Res Commun 341 : 1184-1192, 2006 https://doi.org/10.1016/j.bbrc.2006.01.073
  14. Krygier S, Djakiew D : The neurotrophin receptor p75NTR is a tumor suppressor in human prostate cancer. Anticancer Res 21 : 3749-3755, 2001
  15. Lagadec C, Meignan S, Adriaenssens E, Foveau B, Vanhecke E, Romon R, et al. : TrkA overexpression enhances growth and metastasis of breast cancer cells. Oncogene 28 : 1960-1970, 2009 https://doi.org/10.1038/onc.2009.61
  16. Livak KJ, Schmittgen TD : Analysis of relative gene expression data using real-time quantitative PCR and the $2^{-{\Delta}{\Delta}CT}$ method. Methods 25 : 402-408, 2001 https://doi.org/10.1006/meth.2001.1262
  17. Makkerh JP, Ceni C, Auld DS, Vaillancourt F, Dorval G, Barker PA : p75 neurotrophin receptor reduces ligand-induced Trk receptor ubiquitination and delays Trk receptor internalization and degradation. EMBO Rep 6 : 936-941, 2005 https://doi.org/10.1038/sj.embor.7400503
  18. Martinez-Glez V, Franco-Hernandez C, Alvarez L, de Campos JM., Isla A, Vaquero J, et al. : Meningiomas and schwannomas: molecular subgroup classification found by expression arrays. Int J Oncol 34 : 493-504, 2009
  19. McGregor LM, McCune BK, Graff JR, McDowell PR, Romans KE, Yancopoulos GD, et al. : Roles of trk family neurotrophin receptors in medullary thyroid carcinoma development and progression. Proc Natl Acad Sci U S A 96 : 4540-4545, 1999 https://doi.org/10.1073/pnas.96.8.4540
  20. Miknyoczki SJ, Dionne CA, Klein-Szanto AJ, Ruggeri BA : The novel Trk receptor tyrosine kinase inhibitor CEP-701 (KT-5555) exhibits antitumor efficacy against human pancreatic carcinoma (Panc1) xenograft growth and in vivo invasiveness. Ann N Y Acad Sci 880 : 252-262, 1999 https://doi.org/10.1111/j.1749-6632.1999.tb09530.x
  21. Mitsiadis TA, Pagella P : Expression of nerve growth factor (NGF), TrkA, and p75(NTR) in developing human fetal teeth. Front Physiol 7 : 338, 2016
  22. Mizumura K, Murase S : Role of nerve growth factor in pain. Handb Exp Pharmacol 227 : 57-77, 2015 https://doi.org/10.1007/978-3-662-46450-2_4
  23. Murray SS, Perez P, Lee R, Hempstead BL, Chao MV : A novel p75 neurotrophin receptor-related protein, NRH2, regulates nerve growth factor binding to the TrkA receptor. J Neurosci 24 : 2742- 2749, 2004 https://doi.org/10.1523/JNEUROSCI.3960-03.2004
  24. Nakagawara A, Arima-Nakagawara M, Scavarda NJ, Azar CG, Cantor AB, Brodeur GM : Association between high levels of expression of the TRK gene and favorable outcome in human neuroblastoma. N Engl J Med 328 : 847-854, 1993 https://doi.org/10.1056/NEJM199303253281205
  25. Ricci A, Greco S, Mariotta S, Felici L, Bronzetti E, Cavazzana A, et al. : Neurotrophins and neurotrophin receptors in human lung cancer. Am J Respir Cell Mol Biol 25 : 439-446, 2001 https://doi.org/10.1165/ajrcmb.25.4.4470
  26. Salehi AH, Xanthoudakis S, Barker PA : NRAGE, a p75 neurotrophin receptor-interacting protein, induces caspase activation and cell death through a JNK-dependent mitochondrial pathway. J Biol Chem 277 : 48043-48050, 2002 https://doi.org/10.1074/jbc.M205324200
  27. Skaper SD : The neurotrophin family of neurotrophic factors: an overview. Methods Mol Biol 846 : 1-12, 2012 https://doi.org/10.1007/978-1-61779-536-7_1
  28. Thoenen H, Barde YA : Physiology of nerve growth factor. Physiol Rev 60 : 1284-1335, 1980 https://doi.org/10.1152/physrev.1980.60.4.1284
  29. Tsunoda S, Okumura T, Ito T, Mori Y, Soma T, Watanabe G, et al. : Significance of nerve growth factor overexpression and its autocrine loop in oesophagealsquamous cell carcinoma. Br J Cancer 95 : 322-330, 2006 https://doi.org/10.1038/sj.bjc.6603255
  30. Ullrich A, Gray A, Berman C, Dull TJ : Human $\beta$-nerve growth factor gene sequence highly homologous to that of mouse. Nature 303 : 821-825, 1983 https://doi.org/10.1038/303821a0
  31. Varon S, Nomura J, Shooter EM : The isolation of the mouse nerve growth factor protein in a high molecular weight form. Biochemistry 6 : 2202-2209, 1967 https://doi.org/10.1021/bi00859a043
  32. Wadhwa S, Nag TC, Jindal A, Kushwaha R, Mahapatra AK, Sarkar C : Expression of the neurotrophin receptors Trk A and Trk B in adult human astrocytoma and glioblastoma. J Biosci 28 : 181-188, 2003 https://doi.org/10.1007/BF02706217
  33. Wang X, Ying H, Zhou Z, Hu C, Eisbruch A : Successful treatment of radiation-induced temporal lobe necrosis with mouse nerve growth factor. J Clin Oncol 29 : e166-e168, 2011 https://doi.org/10.1200/JCO.2010.31.7081
  34. Yang T, Wu L, Deng X, Yang C, Xu Y : Clinical features and surgical outcomes of intramedullary schwannomas. Acta Neurochir (Wien) 156 : 1789-1797, 2014 https://doi.org/10.1007/s00701-014-2168-8
  35. Zhang K, Chen S, Lin J, Zhang Y, Yu W, Liu S, et al. : Primary culture of human interspinal schwannoma. J Biomater Tissue Eng 6 : 263-269, 2016 https://doi.org/10.1166/jbt.2016.1445
  36. Zhu ZW, Friess H, Wang L, Bogardus T, Korc M, Kleeff J, et al. : Nerve growth factor exerts differential effects on the growth of human pancreatic cancer cells. Clin Cancer Res 7 : 105-112, 2001
  37. Zong S, Zeng G, Xiong C, Wei B : Treatment results in the differential surgery of intradural extramedullary schwannoma of 110 cases. PLoS One 8 : e63867, 2013 https://doi.org/10.1371/journal.pone.0063867

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