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http://dx.doi.org/10.3340/jkns.2019.0081

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)
Publication Information
Journal of Korean Neurosurgical Society / v.62, no.6, 2019 , pp. 626-634 More about this Journal
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
Schwannoma; Mouse nerve growth factor; TrkA; $p75^{NTR}$;
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1 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   DOI
2 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   DOI
3 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   DOI
4 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
5 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   DOI
6 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   DOI
7 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   DOI
8 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
9 Krygier S, Djakiew D : The neurotrophin receptor p75NTR is a tumor suppressor in human prostate cancer. Anticancer Res 21 : 3749-3755, 2001
10 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   DOI
11 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   DOI
12 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
13 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   DOI
14 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   DOI
15 Gu R, Liu JB, Zhang Q, Liu GY, Zhu QS : MRI diagnosis of intradural extramedullary tumors. J Cancer Res Ther 10 : 927-931, 2014   DOI
16 Mitsiadis TA, Pagella P : Expression of nerve growth factor (NGF), TrkA, and p75(NTR) in developing human fetal teeth. Front Physiol 7 : 338, 2016
17 Mizumura K, Murase S : Role of nerve growth factor in pain. Handb Exp Pharmacol 227 : 57-77, 2015   DOI
18 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   DOI
19 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   DOI
20 George DJ, Suzuki H, Bova GS, Isaacs JT : Mutational analysis of the TrkA gene in prostate cancer. Prostate 36 : 172-180, 1998   DOI
21 Haase G, Pettmann B, Raoul C, Henderson CE : Signaling by death receptors in the nervous system. Curr Opin Neurobiol 18 : 284-291, 2008   DOI
22 Hellebrand EE, Varbiro G : Development of mitochondrial permeability transition inhibitory agents: a novel drug target. Drug Discov Ther 4 : 54-61, 2010
23 Hondermarck H : Neurotrophins and their receptors in breast cancer. Cytokine Growth Factor Rev 23 : 357-365, 2012   DOI
24 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   DOI
25 Johnson TV, Bull ND, Martin KR : Neurotrophic factor delivery as a protective treatment for glaucoma. Exp Eye Res 93 : 196-203, 2011   DOI
26 Friedman WJ : Proneurotrophins, seizures, and neuronal apoptosis. Neuroscientist 16 : 244-252, 2010   DOI
27 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   DOI
28 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   DOI
29 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   DOI
30 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   DOI
31 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   DOI
32 Skaper SD : The neurotrophin family of neurotrophic factors: an overview. Methods Mol Biol 846 : 1-12, 2012   DOI
33 Thoenen H, Barde YA : Physiology of nerve growth factor. Physiol Rev 60 : 1284-1335, 1980   DOI
34 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   DOI
35 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   DOI
36 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   DOI
37 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   DOI