Brevican knockdown reduces late-stage glioma tumor aggressiveness
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Growing evidence supports the important role of the tumor microenvironment (TME) in cancer biology. A defining aspect of the glioma TME is the unique composition and structure of its extracellular matrix (ECM), which enables tumor cells to overcome the inhibitory barriers of the adult central nervous system (CNS). In this way, the TME plays a role in glioma invasion and the cellular heterogeneity that distinguishes these tumors. Brain Enriched Hyaluronan Binding (BEHAB)/brevican (B/b), is a CNS-specific ECM constituent and is upregulated in the glioma TME. Previous studies have shown B/b exerts a pro-invasive function, suggesting it may represent a target to reduce glioma pathogenesis. Herein, we also provide evidence that B/b expression is enriched in the glioma initiating cell (GIC) niche. We demonstrate that B/b plays roles in the pathological progression, aggressiveness, and lethality of tumors derived from human GICs and traditional glioma cell lines. Interestingly, we found that B/b is not required to maintain the defining phenotypic properties of GICs and thereby acts primarily in late stages of glioma progression. This study suggests that the increased expression of B/b in the TME is a valuable therapeutic target for glioma.
KeywordsBrevican Glioma Neural extracellular matrix Proteoglycan Central nervous system
Brain enriched hyaluronan binding/brevican
Central nervous system
Days in vitro
Days post injection
Glioma initiating cell
The authors would like to acknowledge Wendi Burnette for technical assistance with histology and Shieldy Jean-Louis for blinded tumor volume quantification. This work was funded by R01NS035228 (NINDS) and the Joseph C. Georg Fund.
Conflict of interest
The authors declare they have no conflict of interest.
These experiments comply with the ethical standards and current laws of the country in which the research was performed.
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