Tumour cells are the main source of VEGF in GBMs whereas VEGF receptors (VEGFR-1, its soluble form sVEGFR-1, VEGFR-2 and neuropilin-1) are expressed predominantly by endothelial cells.
This enhancer exhibits increased accessibility to DNase I in glioblastoma cell lines that express high levels of VEGF-A but not in several other cell lines that express much lower levels of VEGF-A.
Although no effective treatment option is available for recurrent glioblastomas (GBMs), a subset of patients evidently derived clinical benefit from bevacizumab, a monoclonal antibody against vascular endothelial growth factor.
A strong positive correlation between the mRNA expression levels of HIF-2α, CA9, VEGF, GLUT-1 and OPN suggests a specific hypoxia-associated profile of mRNA expression in glioblastoma multiforme.
The expression of FAT1, EMT (Snail/LOX/Vimentin/N-cad), stemness (SOX2/OCT4/Nestin/REST) and hypoxia markers (HIF-1α/VEGF/PGK1/CA9) was upregulated in ≥39% of GBM tumors (n = 31) with significant positive correlation (p ≤ 0.05) of the expression of FAT1 with LOX/Vimentin/SOX2/HIF-1α/PGK1/VEGF/CA9.
Glioblastoma cancer stem-like cells (GCSCs) promote themselves proliferation by secreting the vascular endothelial growth factor A (VEGF<sub>A</sub>) in an autocrine manner, positively regulated by phosphodiesterase IV (PDE4).
Our results suggest that the interplay between metalloproteinases and VEGF previously described in experimental tumours may also be operative in human GBMs.
In this study, we isolated a small proportion of CD133+ GSCs from the human glioblastoma cell line U87 and found that these GSCs possessed multipotent differentiation potential and released high levels of VEGF as compared with CD133(-) tumour cells.
The development of angiogenesis inhibitor therapy, including treatments targeting vascular endothelial growth factor (VEGF) in particular, raised new hopes for the treatment of GB, but no Phase III clinical trial to date has reported survival benefits relative to standard treatment.
The results from the randomized phase II BELOB trial provided evidence for a potential benefit of bevacizumab (beva), a humanized monoclonal antibody against circulating VEGF-A, when added to CCNU chemotherapy in patients with recurrent glioblastoma (GBM).
The highly vascular malignant brain tumor glioblastoma (GBM) appears to be an ideal target for anti-angiogenic therapy; however, clinical trials to date suggest the VEGF antibody bevacizumab affects only progression-free survival.