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

Authors :
Julian Wurm
Simon P. Behringer
Vidhya M. Ravi
Kevin Joseph
Nicolas Neidert
Julian P. Maier
Roberto Doria-Medina
Marie Follo
Daniel Delev
Dietmar Pfeifer
Jürgen Beck
Roman Sankowski
Oliver Schnell
Dieter H. Heiland
Source :
Cancers, Vol 11, Iss 10, p 1437 (2019)
Publication Year :
2019
Publisher :
MDPI AG, 2019.

Abstract

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.

Details

Language :
English
ISSN :
20726694
Volume :
11
Issue :
10
Database :
Directory of Open Access Journals
Journal :
Cancers
Publication Type :
Academic Journal
Accession number :
edsdoj.7e330f4d644241b183eff76c82b89ec0
Document Type :
article
Full Text :
https://doi.org/10.3390/cancers11101437