The Molecular Biology of Vestibular Schwannomas and Its Association with Hearing Loss: A Review

Celis‐Aguilar, Erika; Lassaletta, Luis; Torres‐Martín, Miguel; Rodrigues, F. Yuri; Nistal, Manuel; Castresana, Javier S.; Gavilán, Javiér; Rey, Juan A.

doi:10.1155/2012/856157

Cited by 25 publications

(23 citation statements)

References 92 publications

(135 reference statements)

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“…VS represents 8% of all primary intracranial tumors (1). Individuals between 30 and 60 years old are the most frequently affected, and there is no gender prevalence (2,3). The majority of VSs are sporadic and, in general, are benign slow-growing neoplasms.…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical profile of cytokines and growth factors expressed in vestibular schwannoma and in normal vestibular nerve tissue

Taurone

Bianchi

Attanasio

et al. 2012

Molecular Medicine Reports

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Vestibular schwannomas, also known as acoustic neuromas, are benign tumors, which originate from myelin-forming Schwann cells. They develop in the vestibular branch of the eighth cranial nerve in the internal auditory canal or cerebellopontine angle. The clinical progression of the condition involves slow and progressive growth, eventually resulting in brainstem compression. The objective of the present study was to investigate the expression level and the localization of the pro-inflammatory cytokines, transforming growth factor-β1 (TGF-β1) interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α), as well as the adhesion molecules, intracellular adhesion molecule-1 and vascular endothelial growth factor (VEGF), in order to determine whether these factors are involved in the transformation and development of human vestibular schwannoma. The present study investigated whether changes in inflammation are involved in tumor growth and if so, the mechanisms underlying this process. The results of the current study demonstrated that pro-inflammatory cytokines, including TGF-β1, IL-1β and IL-6 exhibited increased expression in human vestibular schwannoma tissue compared with normal vestibular nerve samples. TNF-α was weakly expressed in Schwann cells, confirming that a lower level of this cytokine is involved in the proliferation of Schwann cells. Neoplastic Schwann cells produce pro-inflammatory cytokines that may act in an autocrine manner, stimulating cellular proliferation. In addition, the increased expression of VEGF in vestibular schwannoma compared with that in normal vestibular nerve tissue, suggests that this factor may induce neoplastic growth via the promotion of angiogenesis. The present findings suggest that inflammation may promote angiogenesis and consequently contribute to tumor progression. In conclusion, the results of the present study indicated that VEGF and pro-inflammatory cytokines may be potential therapeutic targets in vestibular schwannoma. Further studies are necessary to confirm the involvement of these factors in the growth of neoplasms and to develop inhibitors of pro-inflammatory cytokines as a potential treatment option in the future.

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Section: Introductionmentioning

confidence: 99%

Immunohistochemical profile of cytokines and growth factors expressed in vestibular schwannoma and in normal vestibular nerve tissue

Taurone

Bianchi

Attanasio

et al. 2012

Molecular Medicine Reports

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show abstract

“…Loud noise can damage hearing through acoustic trauma. Whether this could lead to cellular hyperplasia and tumor occurrence is not known, as the biological mechanisms underlying the development of VS are not well understood at present (41,42). VS is generally a slow-growing benign tumor, but other growth patterns are also reported (43,44).…”

Section: Discussionmentioning

confidence: 99%

Exposure to loud noise and risk of vestibular schwannoma: results from the INTERPHONE international case‒control study

Deltour¹,

Schlehofer²,

Massardier-Pilonchéry³

et al. 2018

Scand J Work Environ Health

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“…RBFOX3 encodes a neuron-specific RNA binding protein that is functionally involved in miRNA biogenesis and neuronal developmental differentiation [ 57 , 58 ]. PEX5L is expressed in the brain and its underexpression has been found in vestibular schwannomas associated with hearing loss [ 59 ]. Rab3D is a secretory small GTPase and in vitro and in vivo experiments established its critical function in cancer metastatic processes [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

Microarray Expression Data Identify DCC as a Candidate Gene for Early Meningioma Progression

et al. 2016

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Meningiomas are the most common primary brain tumors bearing in a minority of cases an aggressive phenotype. Although meningiomas are stratified according to their histology and clinical behavior, the underlying molecular genetics predicting aggressiveness are not thoroughly understood. We performed whole transcript expression profiling in 10 grade I and four grade II meningiomas, three of which invaded the brain. Microarray expression analysis identified deleted in colorectal cancer (DCC) as a differentially expressed gene (DEG) enabling us to cluster meningiomas into DCC low expression (3 grade I and 3 grade II tumors), DCC medium expression (2 grade I and 1 grade II tumors), and DCC high expression (5 grade I tumors) groups. Comparison between the DCC low expression and DCC high expression groups resulted in 416 DEGs (p-value < 0.05; fold change > 2). The most significantly downregulated genes in the DCC low expression group comprised DCC, phosphodiesterase 1C (PDE1C), calmodulin-dependent 70kDa olfactomedin 2 (OLFM2), glutathione S-transferase mu 5 (GSTM5), phosphotyrosine interaction domain containing 1 (PID1), sema domain, transmembrane domain (TM) and cytoplasmic domain, (semaphorin) 6D (SEMA6D), and indolethylamine N-methyltransferase (INMT). The most significantly upregulated genes comprised chromosome 5 open reading frame 63 (C5orf63), homeodomain interacting protein kinase 2 (HIPK2), and basic helix-loop-helix family, member e40 (BHLHE40). Biofunctional analysis identified as predicted top upstream regulators beta-estradiol, TGFB1, Tgf beta complex, LY294002, and dexamethasone and as predicted top regulator effectors NFkB, PIK3R1, and CREBBP. The microarray expression data served also for a comparison between meningiomas from female and male patients and for a comparison between brain invasive and non-invasive meningiomas resulting in a number of significant DEGs and related biofunctions. In conclusion, based on its expression levels, DCC may constitute a valid biomarker to identify those benign meningiomas at risk for progression.

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The Molecular Biology of Vestibular Schwannomas and Its Association with Hearing Loss: A Review

Cited by 25 publications

References 92 publications

Immunohistochemical profile of cytokines and growth factors expressed in vestibular schwannoma and in normal vestibular nerve tissue

Immunohistochemical profile of cytokines and growth factors expressed in vestibular schwannoma and in normal vestibular nerve tissue

Exposure to loud noise and risk of vestibular schwannoma: results from the INTERPHONE international case‒control study

Microarray Expression Data Identify DCC as a Candidate Gene for Early Meningioma Progression

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