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.
Highlights
Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults.Due to highly infiltrative growth and invariable recurrence within a short time frame, malignant gliomas are diseases of the entire brain
ELISA assay, where we demonstrated that Chitinase 3-like 1 (CHI3L1) samples, our co-culture model confirmed release of CHI3L1 in co-culture
Our results suggest that reactive transformation of astrocytes in the tumor microenvironment result in increased tumor malignancy
Summary
Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults.Due to highly infiltrative growth and invariable recurrence within a short time frame, malignant gliomas are diseases of the entire brain. In order to respond to pathological alterations of the CNS, astrocytes are able to shift towards reactive states linked to distinct requirements [3]. Multiple reactive states of astrocytes have been reported, mainly associated with neurodegenerative and inflammatory diseases or brain trauma [3,4,5,6,7]. In the context of malignant glioma, astrogliosis at the tumor margin was found to express a distinct reactive pattern which aids in the maintenance of an immunosuppressive microenvironment [6]. This reactive state was marked by high expression of CD274 and the glycoprotein
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
