Vessel co-option in glioblastoma: spy it, find the target and shoot

Giorgio Seano, Amelie Griveau, 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 and David H. Rowitch

Edwin L. Steele Laboratories of Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, USA

Scientific Tracks Abstracts: Arch Cancer Res

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, 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.

Biography :

Giorgio Seano is currently the Head of the Tumor Microenvironment Lab in Institute Curie Research Center, Orsay-Paris (France). He received his PhD in Complex Systems in Life Science in 2010 from University of Turin, Italy. During his PhD training and a Postdoctoral period in Italy, he investigated tumor angiogenesis and integrins and provided the first evidence of a new sub-cellular structure, the endothelial podosome rosette that controls blood vessel branching during sprouting angiogenesis. In 2012, he joined the Laboratory of Dr Rakesh K Jain in Harvard Medical School (Boston) and focused his research on tumor microenvironment, brain tumors and intravital microscopy. Specifically, he intravitally imaged and targeted vessel co-option in glioblastoma. In 2017, he was selected as a Junior Group Leader in Institute Curie and he is now setting up his new laboratory.

E-mail: Giorgio.seano@curie.fr

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