Expression of transforming growth factor-β receptor type 1 and type 2 in human sporadic vestibular Schwannoma

Löttrich, Mathias; Mawrin, Christian; Chamaon, Kathrin; Kirches, Elmar; Dietzmann, Knut; Freigang, B.

doi:10.1016/j.prp.2006.12.007

Cited by 12 publications

(9 citation statements)

References 19 publications

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“…Our results demonstrated that PAK2 was slightly upregulated (1.45-fold, p=0.006805) and TGFβ3 was down-regulated (−8-fold, p=2.25e-5). Moreover, TGFβ1 , TGFβR1 and TGFβR2 were upregulated in schwannomas, in contrast with previous reports, where no evident changes were observed (48). In contrast to PAK2 expression, PAK3 was downregulated (−76-fold, p=4.02e-7) and PAK1 was not affected.…”

Section: Discussioncontrasting

confidence: 99%

Microarray analysis of gene expression in vestibular schwannomas reveals SPP1/MET signaling pathway and androgen receptor deregulation

Torres‐Martín

Lassaletta

San-Román-Montero

et al. 2013

International Journal of Oncology

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Vestibular schwannomas are benign neoplasms that arise from the vestibular nerve. The hallmark of these tumors is the biallelic inactivation of neurofibromin 2 (NF2). Transcriptomic alterations, such as the neuregulin 1 (NRG1)/ErbB2 pathway, have been described in schwannomas. In this study, we performed a whole transcriptome analysis in 31 vestibular schwannomas and 9 control nerves in the Affymetrix Gene 1.0 ST platform, validated by quantitative real-time PCR (qRT-PCR) using TaqMan Low Density arrays. We performed a mutational analysis of NF2 by PCR/denaturing high-performance liquid chromatography (dHPLC) and multiplex ligation-dependent probe amplification (MLPA), as well as a microsatellite marker analysis of the loss of heterozygosity (LOH) of chromosome 22q. The microarray analysis demonstrated that 1,516 genes were deregulated and 48 of the genes were validated by qRT-PCR. At least 2 genetic hits (allelic loss and/or gene mutation) in NF2 were found in 16 tumors, seven cases showed 1 hit and 8 tumors showed no NF2 alteration. MET and associated genes, such as integrin, alpha 4 (ITGA4)/B6, PLEXNB3/SEMA5 and caveolin-1 (CAV1) showed a clear deregulation in vestibular schwannomas. In addition, androgen receptor (AR) downregulation may denote a hormonal effect or cause in this tumor. Furthermore, the osteopontin gene (SPP1), which is involved in merlin protein degradation, was upregulated, which suggests that this mechanism may also exert a pivotal role in schwannoma merlin depletion. Finally, no major differences were observed among tumors of different size, histological type or NF2 status, which suggests that, at the mRNA level, all schwannomas, regardless of their molecular and clinical characteristics, may share common features that can be used in their treatment.

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Section: Discussioncontrasting

confidence: 99%

Microarray analysis of gene expression in vestibular schwannomas reveals SPP1/MET signaling pathway and androgen receptor deregulation

Torres‐Martín

Lassaletta

San-Román-Montero

et al. 2013

International Journal of Oncology

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“…Acute pharyngitis, a common exogenous disease, mainly occurs in the autumn and winter, as well as at the end of spring and the beginning of summer (4). It is generally caused by the decreased local or systemic immunity due to catching a cold, fatigue, or excessive alcohol intake and smoking, which create a favorable condition for pathogenic microorganisms (11).…”

Section: Discussionmentioning

confidence: 99%

“…Acute pharyngitis is a common and frequently-occurring disease, characterized by rapid incidence and development (3). The main causes of acute pharyngitis include bacterial and virus infection, as well as non-infectious factors (such as breathing through the mouth, allergic reaction, gastro-esophageal reflux, smoking, alcohol intake, high temperature, dust, smoke and pungent gas) (4).…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory activity of resveratrol prevents inflammation by inhibiting NF‑κB in animal models of acute pharyngitis

et al. 2017

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Recent studies have demonstrated that resveratrol can reduce blood sugar, improve insulin resistance, regulate abnormalities in lipid metabolism, and lower the secretion and expression of inflammatory factors. The present study investigated the anti‑inflammatory effects of resveratrol in animal models of acute pharyngitis, and its possible mechanisms. Commercial ELISA kits were used to measure tumor necrosis factor‑α, interleukin (IL)‑6, macrophage inflammatory protein‑2, cyclooxygenase‑2 levels and caspase‑3/9 activity. Toll‑like receptor (TLR)‑4, myeloid differentiation primary response protein MyD88, phosphorylated (p)‑nuclear factor (NF)‑κB and p‑IκB were analyzed using western blotting. In a rabbit model of acute pharyngitis, it was demonstrated that resveratrol inhibited tumor necrosis factor‑α and interleukin‑6 serum levels, macrophage inflammatory protein‑2 and cyclooxygenase‑2 activity levels, reactive oxygen species production and caspase‑3/9 activity. Resveratrol suppressed NACHT, LRR and PYD domains‑containing protein 3 and caspase‑1 protein expression, and reduced IL‑1β and IL‑18 protein expression in animal models of acute pharyngitis. Additionally, resveratrol suppressed TLR4 and myeloid differentiation primary response protein 88 protein expression, and reduced p‑NF‑κB and increased p‑IκB protein expression in animal models of acute pharyngitis. In conclusion, these findings indicated that the anti‑inflammatory activity of resveratrol prevents acute pharyngitis‑induced inflammation by inhibiting NF‑κB in animal models. Therefore, these data suggested an important clinical application of resveratrol in preventing acute pharyngitis.

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“…The signalling pathway of TGF-β1 is activated by two transmembrane serine/threonine kinases, TGF-βR1 and TGF-βR2. The type 2 receptor (TGF-βR2) is involved in the antiproliferative activity of TGF-β, whereas the type 1 receptor (TGF-βR1) appears to cause cellular proliferation following cell-matrix interactions (11). Interactions between cytokines and Schwann cells are involved in the development of disorders of the peripheral nervous system.…”

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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Expression of transforming growth factor-β receptor type 1 and type 2 in human sporadic vestibular Schwannoma

Cited by 12 publications

References 19 publications

Microarray analysis of gene expression in vestibular schwannomas reveals SPP1/MET signaling pathway and androgen receptor deregulation

Microarray analysis of gene expression in vestibular schwannomas reveals SPP1/MET signaling pathway and androgen receptor deregulation

Anti-inflammatory activity of resveratrol prevents inflammation by inhibiting NF‑κB in animal models of acute pharyngitis

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

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