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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. Copyright © 2018 Elsevier Inc. All rights reserved.

Citation

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 Suvà, Joanna J Phillips, Manish K Aghi, Shwetal Mehta, Rakesh K Jain, David H Rowitch. A Glial Signature and Wnt7 Signaling Regulate Glioma-Vascular Interactions and Tumor Microenvironment. Cancer cell. 2018 May 14;33(5):874-889.e7

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PMID: 29681511

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