biostudies-literatureUnknown8(1)Scholz AGlioblastoma 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 increEMBO molecular medicine39-57https://www.ebi.ac.uk/biostudies/studies/S-EPMC4718155biostudies-literatureEndothelial cell-derived angiopoietin-2 is a therapeutic target in treatment-naive and bevacizumab-resistant glioblastoma.PMC4718155Meinhardt MFrueh JTUllrich EDeckert MYalcin BHTrojan JTimmer MPlate KHSchittenhelm JReiss YHarter PNBraun CGlas MYamaji MDi Tacchio MSteinbach JPCremer SHerrlinger UGoldbrunner RGurnik SMittelbronn MKrex DSommer KBaumgarten PScholz AWeyerbrock ABahr OfalseEndothelial cell-derived angiopoietin-2 is a therapeutic target in treatment-naive and bevacizumab-resistant glioblastoma.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 incre2016-01-01T00:00:00Z2016 Jan2025-04-18T16:28:36.82Z2019-03-27T02:07:07ZS-EPMC47181552666626910.15252/emmm.201505505