Inhibition of MEK pathway in vestibular schwannoma cell culture

Neff, Brian A.; Voss, Stephen G.; Schmitt, William R.; Driscoll, Colin L. W.; Link, Michael J.; Beatty, Charles W.; Kita, Hirohito

doi:10.1002/lary.23472

Cited by 11 publications

(11 citation statements)

References 31 publications

(38 reference statements)

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“…According to the results of KEGG enrichment analyses, 335 pathways were included among the differentially expressed proteins, and 21 of these pathways were significantly enriched. Although some pathways have been suggested to be enriched in VS, such as the SPP1/MET, MEK, VEGF, and RAC/JNK signaling pathways, our protein–protein interaction networks did not show that these pathways were enriched in our VS samples.…”

Section: Discussioncontrasting

confidence: 64%

“…Merlin mediates contact inhibition‐dependent cell growth through its interaction with CD44, and these interactions might function as a switch controlling cell growth arrest and cell proliferation . Merlin's tumor‐suppressor function is also linked to various cellular pathways such as the integrin‐mediated Rac pathway, the Wnt pathway, the Hippo pathway, and Ras/Raf/MEK/ERK . In addition to dysfunction of Merlin, other proteins might play important roles in the tumorigenesis of VS.…”

Section: Introductionmentioning

confidence: 99%

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Identification of Predictive Proteins and Biological Pathways for the Tumorigenicity of Vestibular Schwannoma by Proteomic Profiling

Zhang

Shi

et al. 2019

Proteomics Clinical Apps

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Purpose Vestibular schwannomas (VSs) are benign tumors that account for 8–10% of all intracranial tumors. So far, the tumorigenesis of VS has not been fully elucidated. This study is designed to identify differently expressed proteins involved in VS tumorigenesis. Experimental Design An isobaric tag is used for relative and absolute quantification (iTRAQ) approach to characterize the protein expression profiles from pooled VS tissues (n = 12) and pooled matched normal vestibular tissues (n = 12). Results A total of 933 differentially expressed proteins are identified between VS and the matched normal vestibular tissues, with 489 being upregulated and 444 being downregulated. Bioinformatics analyses are performed according to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Several of the differentially expressed proteins are validated by western blotting analyses, and upregulation of LGALS1, ANXA1, GRB2, and STAT1 is validated in VS tissue by immunohistochemistry. Conclusions and Clinical Relevance The study represents the successful application of iTRAQ technology to an investigation of VS. Many of the differentially expressed proteins identified here have not been linked to VS before, and these dysregulated proteins may provide potential biomarkers for human VS diagnosis.

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Section: Discussioncontrasting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Identification of Predictive Proteins and Biological Pathways for the Tumorigenicity of Vestibular Schwannoma by Proteomic Profiling

Zhang

Shi

et al. 2019

Proteomics Clinical Apps

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“…Intracellularly, merlin regulates the growth factor receptor-induced activation of the small G proteins Ras and Rac, which in turn activate mitogen-activated protein kinase (MAPK) signaling [ 48 , 51 ]. Targeting MAPK signaling, e.g., by MEK inhibitors, therefore appears to be another therapeutic option deserving of future investigation, according to several preclinical studies [ 52 , 53 ].…”

Section: Merlin-dependent Signaling Pathways and Potential Targets Fomentioning

confidence: 99%

Pathomechanisms in schwannoma development and progression

2020

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Schwannomas are tumors of the peripheral nervous system, consisting of different cell types. These include tumorigenic Schwann cells, axons, macrophages, T cells, fibroblasts, blood vessels, and an extracellular matrix. All cell types involved constitute an intricate “tumor microenvironment” and play relevant roles in the development and progression of schwannomas. Although Nf2 tumor suppressor gene-deficient Schwann cells are the primary tumorigenic element and principle focus of current research efforts, evidence is accumulating regarding the contributory roles of other cell types in schwannoma pathology. In this review, we aim to provide an overview of intra- and intercellular mechanisms contributing to schwannoma formation. “Genes load the gun, environment pulls the trigger.” -George A. Bray

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“…Primary cultures derived from human VS are established in a similar manner as SCs to prevent fibroblast contamination (Nair, Leung, Collins, Ramsden, & Wilson, 2007), using methods that may alter VS pathobiology. Further, those who have successfully cultured VS cells have not characterized these cultures over time (Bush et al, 2012; Neff et al, 2012). …”

Section: Introductionmentioning

confidence: 99%

Primary culture of human Schwann and schwannoma cells: Improved and simplified protocol

et al. 2014

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Primary culture of human Schwann cells (SCs) and vestibular schwannoma (VS) cells are invaluable tools to investigate SC physiology and VS pathobiology, and to devise effective pharmacotherapies against VS, which are sorely needed. However, existing culture protocols, in aiming to create robust, pure cultures, employ methods that can lead to loss of biological characteristics of the original cells, potentially resulting in misleading biological findings. We have developed a minimally manipulative method to culture primary human SC and VS cells, without the use of selective mitogens, toxins, or time-consuming and potentially transformative laboratory techniques. Schwann cell purity was quantified longitudinally using S100 staining in SC cultures derived from the great auricular nerve and VS cultures followed for 7 and 12 weeks, respectively. SC cultures retained approximately ≥85% purity for 2 weeks. VS cultures retained approximately ≥80% purity for the majority of the span of 12 weeks, with maximal purity of 87% at 2 weeks. The VS cultures showed high level of biological similarity (68% on average) to their respective parent tumors, as assessed using a protein array featuring 41 growth factors and receptors. Apoptosis rate in vitro negatively correlated with tumor volume. Our results, obtained using a faster, simplified culturing method than previously utilized, indicate that highly pure, primary human SC and VS cultures can be established with minimal manipulation, reaching maximal purity at 2 weeks of culture. The VS cultures recapitulate the parent tumors' biology to a great degree, making them relevant models to investigate VS pathobiology.

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Inhibition of MEK pathway in vestibular schwannoma cell culture

Cited by 11 publications

References 31 publications

Identification of Predictive Proteins and Biological Pathways for the Tumorigenicity of Vestibular Schwannoma by Proteomic Profiling

Identification of Predictive Proteins and Biological Pathways for the Tumorigenicity of Vestibular Schwannoma by Proteomic Profiling

Pathomechanisms in schwannoma development and progression

Primary culture of human Schwann and schwannoma cells: Improved and simplified protocol

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