Endothelial cell-derived angiopoietin-2 is a therapeutic target in treatment-naive and bevacizumab-resistant glioblastoma
| العنوان: | Endothelial cell-derived angiopoietin-2 is a therapeutic target in treatment-naive and bevacizumab-resistant glioblastoma |
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| المؤلفون: | Christian Braun, Martina Deckert, Mariangela Di Tacchio, Joachim P. Steinbach, Yvonne Reiss, Jochen T. Frueh, Martin Glas, Dietmar Krex, Burak Hasan Yalcin, Jörg Trojan, Evelyn Ullrich, Ulrich Herrlinger, Peter Baumgarten, Jens Schittenhelm, Alexander Scholz, Sebastian Cremer, Patrick N. Harter, Kathleen Sommer, Oliver Bähr, Matthias Meinhardt, Stefanie Gurnik, Roland Goldbrunner, Astrid Weyerbrock, Michel Mittelbronn, Karl H. Plate, Marco Timmer, Maiko Yamaji |
| المصدر: | ResearcherID EMBO Molecular Medicine |
| مصطلحات موضوعية: | 0301 basic medicine, Vascular Endothelial Growth Factor A, Pathology, Myeloid, Mice, Medicine, Research Articles, Cancer, Brain Neoplasms, Brain, Up-Regulation, Endothelial stem cell, Bevacizumab, Vascular endothelial growth factor A, medicine.anatomical_structure, Molecular Medicine, Female, Mannose Receptor, medicine.drug, Signal Transduction, Research Article, medicine.medical_specialty, Endothelium, therapy resistance, Recombinant Fusion Proteins, macrophage polarization, Macrophage polarization, anti‐angiogenic therapy, Mice, Transgenic, Receptors, Cell Surface, Angiopoietin-2, 03 medical and health sciences, Downregulation and upregulation, Animals, Humans, Lectins, C-Type, Pharmacology & Drug Discovery, ddc:610, business.industry, Macrophages, glioblastoma, Endothelial Cells, tumor angiogenesis, Blockade, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Mannose-Binding Lectins, Receptors, Vascular Endothelial Growth Factor, Drug Resistance, Neoplasm, Cancer research, Neoplasm Grading, business, Neuroscience |
| الوصف: | Glioblastoma multiforme (GBM) is treated by surgical resection followed by radiochemotherapy. Bevacizumab is commonly deployed for anti‐angiogenic therapy of recurrent GBM; however, innate immune cells have been identified as instigators of resistance to bevacizumab treatment. We identified angiopoietin‐2 (Ang‐2) as a potential target in both naive and bevacizumab‐treated glioblastoma. Ang‐2 expression was absent in normal human brain endothelium, while the highest Ang‐2 levels were observed in bevacizumab‐treated GBM. In a murine GBM model, VEGF blockade resulted in endothelial upregulation of Ang‐2, whereas the combined inhibition of VEGF and Ang‐2 leads to extended survival, decreased vascular permeability, depletion of tumor‐associated macrophages, improved pericyte coverage, and increased numbers of intratumoral T lymphocytes. CD206+ (M2‐like) macrophages were identified as potential novel targets following anti‐angiogenic therapy. Our findings imply a novel role for endothelial cells in therapy resistance and identify endothelial cell/myeloid cell crosstalk mediated by Ang‐2 as a potential resistance mechanism. Therefore, combining VEGF blockade with inhibition of Ang‐2 may potentially overcome resistance to bevacizumab therapy. |
| وصف الملف: | application/pdf |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3bcab0620b92991bdc0bf1f05c0fb497Test http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000368135800005&KeyUID=WOS:000368135800005Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3bcab0620b92991bdc0bf1f05c0fb497 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |