Title

A Glial Signature And Wnt7 Signaling Regulate Glioma-Vascular Interactions And Tumor Microenvironment

Department

neurobiology

Document Type

Article

Abstract

Gliomas comprise heterogeneous malignant glial and stromal cells. While blood vessel co-option is a potential mechanism to escape anti-angiogenic therapy, the relevance of glial phenotype in this process is unclear. We show that Olig2+ oligodendrocyte precursor-like glioma cells invade by single-cell vessel co-option and preserve the blood-brain barrier (BBB). Conversely, Olig2-negative glioma cells form dense perivascular collections and promote angiogenesis and BBB breakdown, leading to innate immune cell activation. Experimentally, Olig2 promotes Wnt7b expression, a finding that correlates in human glioma profiling. Targeted Wnt7a/7b deletion or pharmacologic Wnt inhibition blocks Olig2+ glioma single-cell vessel co-option and enhances responses to temozolomide. Finally, Olig2 and Wnt7 become upregulated after anti-VEGF treatment in preclinical models and patients. Thus, glial-encoded pathways regulate distinct glioma-vascular microenvironmental interactions. Griveau et al. show that Olig2+ glioma cells invade by single-cell vessel co-option, whereas Olig2− glioma cells promote angiogenesis and that anti-VEGF treatment selects for the Olig2+/Wnt7+ phenotype. Wnt7 is necessary for vessel co-option, and Wnt inhibition enhances the response to temozolomide treatment.

Publication Date

5-14-2018

Publication Title

Cancer Cell

ISSN

15356108

Volume

33

Issue

5

First Page

874

Last Page

8890000000

Digital Object Identifier (DOI)

10.1016/j.ccell.2018.03.020

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