PortalPublikationenThe importance of nerve microenvironment for schwannoma deve...

The importance of nerve microenvironment for schwannoma development

Standard

The importance of nerve microenvironment for schwannoma development. / Schulz, Alexander; Büttner, Robert; Hagel, Christian; Baader, Stephan L; Kluwe, Lan; Salamon, Johannes; Mautner, Victor-Felix; Mindos, Thomas; Parkinson, David B; Gehlhausen, Jeffrey R; Clapp, D Wade; Morrison, Helen.

in: ACTA NEUROPATHOL, Jahrgang 132, Nr. 2, 28.05.2016, S. 289-307.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Schulz, A, Büttner, R, Hagel, C, Baader, SL, Kluwe, L, Salamon, J, Mautner, V-F, Mindos, T, Parkinson, DB, Gehlhausen, JR, Clapp, DW & Morrison, H 2016, 'The importance of nerve microenvironment for schwannoma development', ACTA NEUROPATHOL, Jg. 132, Nr. 2, S. 289-307. https://doi.org/10.1007/s00401-016-1583-8

APA

Schulz, A., Büttner, R., Hagel, C., Baader, S. L., Kluwe, L., Salamon, J., Mautner, V-F., Mindos, T., Parkinson, D. B., Gehlhausen, J. R., Clapp, D. W., & Morrison, H. (2016). The importance of nerve microenvironment for schwannoma development. ACTA NEUROPATHOL, 132(2), 289-307. https://doi.org/10.1007/s00401-016-1583-8

Vancouver

Schulz A, Büttner R, Hagel C, Baader SL, Kluwe L, Salamon J et al. The importance of nerve microenvironment for schwannoma development. ACTA NEUROPATHOL. 2016 Mai 28;132(2):289-307. https://doi.org/10.1007/s00401-016-1583-8

Bibtex

@article{42ded9b7de8e4bc096f4ee2b56ab8ce7,
title = "The importance of nerve microenvironment for schwannoma development",
abstract = "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.",
author = "Alexander Schulz and Robert B{\"u}ttner and Christian Hagel and Baader, {Stephan L} and Lan Kluwe and Johannes Salamon and Victor-Felix Mautner and Thomas Mindos and Parkinson, {David B} and Gehlhausen, {Jeffrey R} and Clapp, {D Wade} and Helen Morrison",
year = "2016",
month = may,
day = "28",
doi = "10.1007/s00401-016-1583-8",
language = "English",
volume = "132",
pages = "289--307",
journal = "ACTA NEUROPATHOL",
issn = "0001-6322",
publisher = "Springer",
number = "2",

}

RIS

TY - JOUR

T1 - The importance of nerve microenvironment for schwannoma development

AU - Schulz, Alexander

AU - Büttner, Robert

AU - Hagel, Christian

AU - Baader, Stephan L

AU - Kluwe, Lan

AU - Salamon, Johannes

AU - Mautner, Victor-Felix

AU - Mindos, Thomas

AU - Parkinson, David B

AU - Gehlhausen, Jeffrey R

AU - Clapp, D Wade

AU - Morrison, Helen

PY - 2016/5/28

Y1 - 2016/5/28

N2 - 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.

AB - 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.

U2 - 10.1007/s00401-016-1583-8

DO - 10.1007/s00401-016-1583-8

M3 - SCORING: Journal article

C2 - 27236462

VL - 132

SP - 289

EP - 307

JO - ACTA NEUROPATHOL

JF - ACTA NEUROPATHOL

SN - 0001-6322

IS - 2

ER -