The effects of VEGF and SDF-1 on U251n cell invasion and proliferation were measured using inhibitors to VEGF receptor1 and receptor2, DC101 and MF1, respectively, and a CXCR4 antagonist (AMD3100).
These data suggest that prolonged hypoxia promotes the expression and functional activation of AMPKalpha2 and VEGF production in glioma cell lines and glioblastoma multiform tumors, thus contributing to tumor survival and angiogenesis in high grade human gliomas.
FGF1 was equally expressed in the vast majority of tumours, whereas S100A13 and VEGF-A were significantly up-regulated in high-grade vascularized gliomas.
We compared the effect of inhibiting IL6 and VEGF on U87-derived experimental glioma grown on the chick chorio-allantoic membrane (CAM) or in the brain of xenografted mice.
Hemin elevated both HO-1 and VEGF mRNA levels in the glioma cells at the concentration causing no critical damage to the cells, and the elevation of BDNF mRNA levels was also observed by exposing the cells to hemin under the same conditions.
Loss of the tumor-suppressor PTEN and activation of the receptor tyrosine kinases (RTKs) EGF receptor, c-Met, PDGF receptor and VEGF receptor are among the most common molecular dysfunctions associated with glioma malignancy.
In a human glioma model, inhibition of IRE1alpha correlated with down-regulation of prevalent proangiogenic factors such as VEGF-A, IL-1beta, IL-6, and IL-8.
In the glioma cell line U251HF, we further determined that blocking the PI3K/Akt signaling pathway with either adenoviral-mediated PTEN expression or LY294002 enhanced PAX6-mediated suppression of VEGFA in an additive manner; thus, PAX6-mediated suppression of VEGFA is not via the canonical pathway through HIF1A.
Conversely, RNA interference-mediated knockdown of US28 in human glioma cells persistently infected with HCMV led to an inhibition in VEGF expression and glioma cell invasion in response to CCL5 stimulation.
However, contrary to its reported antiangiogenic effects, treatment with celecoxib actually induced the expression of VEGF in multiple glioma as well as other cancer cell lines.
In human primary glioma specimens, expression of Nodal positively correlates with WHO glioma tumor grades and expression of VEGF in the corresponding glioma specimens.
Our observations support the hypothesis that IDH1 mutation may correlate with the benefit from VEGF(R)- versus EGFR-targeted therapy at the time of recurrence in glioma patients.