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

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2018 Apr 24

PMID 29681511

Citations 126

Authors

Amelie Griveau

Giorgio Seano

Samuel J Shelton

Robert Kupp

Arman Jahangiri

Kirsten Obernier

Shanmugarajan Krishnan

Olle R Lindberg

Tracy J Yuen

An-Chi Tien

Jennifer K Sabo

Nancy Wang

Ivy Chen

Jonas Kloepper

Louis Larrouquere

Mitrajit Ghosh

Itay Tirosh

Emmanuelle Huillard

Arturo Alvarez-Buylla

Michael C Oldham

Anders I Persson

William A Weiss

Tracy T Batchelor

Anat Stemmer-Rachamimov

Mario L Suva

Joanna J Phillips

Manish K Aghi

Shwetal Mehta

Rakesh K Jain

David H Rowitch

Affiliations

Soon will be listed here.

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.

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