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Astrogliosis Releases Pro-Oncogenic Chitinase 3-Like 1 Causing MAPK Signaling in Glioblastoma

Although reactive astrocytes constitute a major component of the cellular environment in glioblastoma, their function and crosstalk to other components of the environment is still poorly understood. Gene expression analysis of purified astrocytes from both the tumor core and non-infiltrated cortex r...

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Autores principales: Wurm, Julian, Behringer, Simon P., Ravi, Vidhya M., Joseph, Kevin, Neidert, Nicolas, Maier, Julian P., Doria-Medina, Roberto, Follo, Marie, Delev, Daniel, Pfeifer, Dietmar, Beck, Jürgen, Sankowski, Roman, Schnell, Oliver, Heiland, Dieter H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826948/
https://www.ncbi.nlm.nih.gov/pubmed/31561550
http://dx.doi.org/10.3390/cancers11101437
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author Wurm, Julian
Behringer, Simon P.
Ravi, Vidhya M.
Joseph, Kevin
Neidert, Nicolas
Maier, Julian P.
Doria-Medina, Roberto
Follo, Marie
Delev, Daniel
Pfeifer, Dietmar
Beck, Jürgen
Sankowski, Roman
Schnell, Oliver
Heiland, Dieter H.
author_facet Wurm, Julian
Behringer, Simon P.
Ravi, Vidhya M.
Joseph, Kevin
Neidert, Nicolas
Maier, Julian P.
Doria-Medina, Roberto
Follo, Marie
Delev, Daniel
Pfeifer, Dietmar
Beck, Jürgen
Sankowski, Roman
Schnell, Oliver
Heiland, Dieter H.
author_sort Wurm, Julian
collection PubMed
description Although reactive astrocytes constitute a major component of the cellular environment in glioblastoma, their function and crosstalk to other components of the environment is still poorly understood. Gene expression analysis of purified astrocytes from both the tumor core and non-infiltrated cortex reveals a tumor-related up-regulation of Chitinase 3-like 1 (CHI3L1), a cytokine which is related to inflammation, extracellular tissue remodeling, and fibrosis. Further, we established and validated a co-culture model to investigate the impact of reactive astrocytes within the tumor microenvironment. Here we show that reactive astrocytes promote a subtype-shift of glioblastoma towards the mesenchymal phenotype, driving mitogen-activated protein kinases (MAPK) signaling as well as increased proliferation and migration. In addition, we demonstrate that MAPK signaling is directly caused by a CHI3L1-IL13RA2 co-binding, which leads to increased downstream MAPK and AKT signaling. This novel microenvironmental crosstalk highlights the crucial role of non-neoplastic cells in malignant brain tumors and opens up new perspectives for targeted therapies in glioblastoma.
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spelling pubmed-68269482019-11-18 Astrogliosis Releases Pro-Oncogenic Chitinase 3-Like 1 Causing MAPK Signaling in Glioblastoma Wurm, Julian Behringer, Simon P. Ravi, Vidhya M. Joseph, Kevin Neidert, Nicolas Maier, Julian P. Doria-Medina, Roberto Follo, Marie Delev, Daniel Pfeifer, Dietmar Beck, Jürgen Sankowski, Roman Schnell, Oliver Heiland, Dieter H. Cancers (Basel) Article Although reactive astrocytes constitute a major component of the cellular environment in glioblastoma, their function and crosstalk to other components of the environment is still poorly understood. Gene expression analysis of purified astrocytes from both the tumor core and non-infiltrated cortex reveals a tumor-related up-regulation of Chitinase 3-like 1 (CHI3L1), a cytokine which is related to inflammation, extracellular tissue remodeling, and fibrosis. Further, we established and validated a co-culture model to investigate the impact of reactive astrocytes within the tumor microenvironment. Here we show that reactive astrocytes promote a subtype-shift of glioblastoma towards the mesenchymal phenotype, driving mitogen-activated protein kinases (MAPK) signaling as well as increased proliferation and migration. In addition, we demonstrate that MAPK signaling is directly caused by a CHI3L1-IL13RA2 co-binding, which leads to increased downstream MAPK and AKT signaling. This novel microenvironmental crosstalk highlights the crucial role of non-neoplastic cells in malignant brain tumors and opens up new perspectives for targeted therapies in glioblastoma. MDPI 2019-09-26 /pmc/articles/PMC6826948/ /pubmed/31561550 http://dx.doi.org/10.3390/cancers11101437 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wurm, Julian
Behringer, Simon P.
Ravi, Vidhya M.
Joseph, Kevin
Neidert, Nicolas
Maier, Julian P.
Doria-Medina, Roberto
Follo, Marie
Delev, Daniel
Pfeifer, Dietmar
Beck, Jürgen
Sankowski, Roman
Schnell, Oliver
Heiland, Dieter H.
Astrogliosis Releases Pro-Oncogenic Chitinase 3-Like 1 Causing MAPK Signaling in Glioblastoma
title Astrogliosis Releases Pro-Oncogenic Chitinase 3-Like 1 Causing MAPK Signaling in Glioblastoma
title_full Astrogliosis Releases Pro-Oncogenic Chitinase 3-Like 1 Causing MAPK Signaling in Glioblastoma
title_fullStr Astrogliosis Releases Pro-Oncogenic Chitinase 3-Like 1 Causing MAPK Signaling in Glioblastoma
title_full_unstemmed Astrogliosis Releases Pro-Oncogenic Chitinase 3-Like 1 Causing MAPK Signaling in Glioblastoma
title_short Astrogliosis Releases Pro-Oncogenic Chitinase 3-Like 1 Causing MAPK Signaling in Glioblastoma
title_sort astrogliosis releases pro-oncogenic chitinase 3-like 1 causing mapk signaling in glioblastoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826948/
https://www.ncbi.nlm.nih.gov/pubmed/31561550
http://dx.doi.org/10.3390/cancers11101437
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