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A Glial Signature and Wnt7 Signaling Regulate Glioma-Vascular Interactions and Tumor Microenvironment.
Griveau, Amelie; Seano, Giorgio; Shelton, Samuel J; Kupp, Robert; Jahangiri, Arman; Obernier, Kirsten; Krishnan, Shanmugarajan; Lindberg, Olle R; Yuen, Tracy J; Tien, An-Chi; Sabo, Jennifer K; Wang, Nancy; Chen, Ivy; Kloepper, Jonas; Larrouquere, Louis; Ghosh, Mitrajit; Tirosh, Itay; Huillard, Emmanuelle; Alvarez-Buylla, Arturo; Oldham, Michael C; Persson, Anders I; Weiss, William A; Batchelor, Tracy T; Stemmer-Rachamimov, Anat; Suvà, Mario L; Phillips, Joanna J; Aghi, Manish K; Mehta, Shwetal; Jain, Rakesh K; Rowitch, David H.
Afiliação
  • Griveau A; Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
  • Seano G; Edwin L. Steele Laboratories of Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Shelton SJ; Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, University of California San Francisco, San Francisco, CA 94143, USA; Department of Neurological Surgery and Brain Tumor Research Center, University of California San Francisco, San Francisco, CA 94143, USA.
  • Kupp R; Barrow Neurological Institute, Saint Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA.
  • Jahangiri A; Department of Neurological Surgery and Brain Tumor Research Center, University of California San Francisco, San Francisco, CA 94143, USA.
  • Obernier K; Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, University of California San Francisco, San Francisco, CA 94143, USA; Department of Neurological Surgery and Brain Tumor Research Center, University of California San Francisco, San Francisco, CA 94143, USA.
  • Krishnan S; Edwin L. Steele Laboratories of Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Lindberg OR; Department of Neurological Surgery and Brain Tumor Research Center, University of California San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94143, USA.
  • Yuen TJ; Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
  • Tien AC; Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
  • Sabo JK; Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
  • Wang N; Edwin L. Steele Laboratories of Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Chen I; Edwin L. Steele Laboratories of Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Kloepper J; Edwin L. Steele Laboratories of Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Larrouquere L; Edwin L. Steele Laboratories of Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Ghosh M; Edwin L. Steele Laboratories of Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Tirosh I; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Huillard E; ICM Brain and Spine Institute, 47 Boulevard de l'Hopital, 75013 Paris, France.
  • Alvarez-Buylla A; Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, University of California San Francisco, San Francisco, CA 94143, USA; Department of Neurological Surgery and Brain Tumor Research Center, University of California San Francisco, San Francisco, CA 94143, USA.
  • Oldham MC; Department of Neurological Surgery and Brain Tumor Research Center, University of California San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94143, USA.
  • Persson AI; Department of Neurological Surgery and Brain Tumor Research Center, University of California San Francisco, San Francisco, CA 94143, USA; Department of Neurology, University of California San Francisco, San Francisco, CA 94143, USA; Sandler Neurosciences Center, University of California San Francisc
  • Weiss WA; Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143, USA; Department of Neurological Surgery and Brain Tumor Research Center, University of California San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of Cal
  • Batchelor TT; Stephen E. and Catherine Pappas Center for Neuro-Oncology, Department of Neurology and Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Stemmer-Rachamimov A; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Suvà ML; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Phillips JJ; Department of Neurological Surgery and Brain Tumor Research Center, University of California San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94143, USA; Department of Pathology, University of Cali
  • Aghi MK; Department of Neurological Surgery and Brain Tumor Research Center, University of California San Francisco, San Francisco, CA 94143, USA.
  • Mehta S; Barrow Neurological Institute, Saint Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA.
  • Jain RK; Edwin L. Steele Laboratories of Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Electronic address: jain@steele.mgh.harvard.edu.
  • Rowitch DH; Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, University of California San Francisco, San Francisco, CA 94143, USA; Department of Neurological Surgery and Brain Tumor Re
Cancer Cell ; 33(5): 874-889.e7, 2018 05 14.
Article em En | MEDLINE | ID: mdl-29681511
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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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Oligodendroglia / Proteínas Wnt / Fator de Transcrição 2 de Oligodendrócitos / Glioma Idioma: En Ano de publicação: 2018 Tipo de documento: Article
Texto completo
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PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Oligodendroglia / Proteínas Wnt / Fator de Transcrição 2 de Oligodendrócitos / Glioma Idioma: En Ano de publicação: 2018 Tipo de documento: Article