Download
The importance of nerve microenvironment for schwannoma development.pdf 11,25MB
WeightNameValue
1000 Titel
  • The importance of nerve microenvironment for schwannoma development
1000 Autor/in
  1. Schulz, Alexander |
  2. Büttner, Robert |
  3. Hagel, Christian |
  4. Baader, Stephan L. |
  5. Kluwe, Lan |
  6. Salamon, Johannes |
  7. Mautner, Victor-Felix |
  8. Mindos, Thomas |
  9. Parkinson, David B. |
  10. Gehlhausen, Jeffrey R. |
  11. Clapp, D. Wade |
  12. Morrison, Helen |
1000 Erscheinungsjahr 2016
1000 Art der Datei
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2016-05-28
1000 Erschienen in
1000 Quellenangabe
  • 132(2): 289-307
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2016
1000 Lizenz
1000 Verlagsversion
  • http://doi.org/10.1007/s00401-016-1583-8 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947119/ |
1000 Ergänzendes Material
  • https://link.springer.com/article/10.1007%2Fs00401-016-1583-8 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Schwannomas are predominantly benign nerve sheath neoplasms caused by Nf2 gene inactivation. Presently, treatment options are mainly limited to surgical tumor resection due to the lack of effective pharmacological drugs. Although the mechanistic understanding of Nf2 gene function has advanced, it has so far been primarily restricted to Schwann cell-intrinsic events. Extracellular cues determining Schwann cell behavior with regard to schwannoma development remain unknown. Here we show pro-tumourigenic microenvironmental effects on Schwann cells where an altered axonal microenvironment in cooperation with injury signals contribute to a persistent regenerative Schwann cell response promoting schwannoma development. Specifically in genetically engineered mice following crush injuries on sciatic nerves, we found macroscopic nerve swellings in mice with homozygous nf2 gene deletion in Schwann cells and in animals with heterozygous nf2 knockout in both Schwann cells and axons. However, patient-mimicking schwannomas could only be provoked in animals with combined heterozygous nf2 knockout in Schwann cells and axons. We identified a severe re-myelination defect and sustained macrophage presence in the tumor tissue as major abnormalities. Strikingly, treatment of tumor-developing mice after nerve crush injury with medium-dose aspirin significantly decreased schwannoma progression in this disease model. Our results suggest a multifactorial concept for schwannoma formation—emphasizing axonal factors and mechanical nerve irritation as predilection site for schwannoma development. Furthermore, we provide evidence supporting the potential efficacy of anti-inflammatory drugs in the treatment of schwannomas.
1000 Sacherschließung
lokal Tumor induction
lokal NF2M
lokal tissue inflammation
lokal Microenvironment
lokal Neurofibromatosis type 2
lokal Crush injury
lokal Sciatic nerve
lokal Schwannoma
1000 Fachgruppe
  1. Biologie |
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. http://orcid.org/0000-0003-1604-4596|http://orcid.org/0000-0002-4337-4251|https://frl.publisso.de/adhoc/creator/SGFnZWwsIENocmlzdGlhbg==|https://frl.publisso.de/adhoc/creator/QmFhZGVyLCBTdGVwaGFuIEwu|https://frl.publisso.de/adhoc/creator/S2x1d2UsIExhbg==|https://frl.publisso.de/adhoc/creator/U2FsYW1vbiwgSm9oYW5uZXM=|https://frl.publisso.de/adhoc/creator/TWF1dG5lciwgVmljdG9yLUZlbGl4|https://frl.publisso.de/adhoc/creator/TWluZG9zLCBUaG9tYXM=|https://frl.publisso.de/adhoc/creator/UGFya2luc29uLCBEYXZpZCBCLg==|https://frl.publisso.de/adhoc/creator/R2VobGhhdXNlbiwgSmVmZnJleSBSLg==|https://frl.publisso.de/adhoc/creator/Q2xhcHAsIEQuIFdhZGU=|http://orcid.org/0000-0003-4938-1409
1000 Label
1000 Förderer
  1. Deutsche Forschungsgemeinschaft (DFG) |
  2. Deutsche Krebshilfe |
  3. Children’s Tumor Foundation |
1000 Fördernummer
  1. SFB 604; MO 1421/2-1; RTG1715
  2. 107089
  3. 2015-05-010
1000 Förderprogramm
  1. -
  2. -
  3. Drug Discovery Initiative Award
1000 Dateien
  1. The importance of nerve microenvironment for schwannoma development
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft (DFG) |
    1000 Förderprogramm -
    1000 Fördernummer SFB 604; MO 1421/2-1; RTG1715
  2. 1000 joinedFunding-child
    1000 Förderer Deutsche Krebshilfe |
    1000 Förderprogramm -
    1000 Fördernummer 107089
  3. 1000 joinedFunding-child
    1000 Förderer Children’s Tumor Foundation |
    1000 Förderprogramm Drug Discovery Initiative Award
    1000 Fördernummer 2015-05-010
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6403876.rdf
1000 Erstellt am 2017-08-15T10:16:02.454+0200
1000 Erstellt von 122
1000 beschreibt frl:6403876
1000 Bearbeitet von 218
1000 Zuletzt bearbeitet Thu Jan 30 15:44:26 CET 2020
1000 Objekt bearb. Wed Mar 07 12:43:49 CET 2018
1000 Vgl. frl:6403876
1000 Oai Id
  1. oai:frl.publisso.de:frl:6403876 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

View source