In situ hybridization (ISH) and immunohistochemistry (IHC) were used to detect vascular endothelial growth factor (VEGF) mRNA and protein expression in sections of glioma xenografts and spheroids in which hypoxic regions and regions with well-oxygenated necrosis were identified on contiguous sections by use of the hypoxia-specific marker, 3H-misonidazole.
We found that HULC, vascular endothelial growth factor (VEGF), and ESM-1 (endothelial cell specific molecule 1) expression and microvessel density were positively correlated with grade dependency in glioma patient tissues, and that HULC silencing suppressed angiogenesis by inhibiting glioma cells proliferation and invasion.
In vitro transfection with pre-miR-93 and antagomiR-93 inversely modulated VEGF and IL-8 gene expression and protein release when the glioma cell line U251 was considered.
Two mechanisms of bevacizumab-induced MIF reduction were identified: (1) bevacizumab bound MIF and blocked MIF-induced M1 polarization of macrophages; and (2) VEGF increased glioma MIF production in a VEGFR2-dependent manner, suggesting that bevacizumab-induced VEGF depletion would downregulate MIF.
Our findings link pleiotrophin abundance in gliomas with survival in humans and mice, and show that pleiotrophin promotes glioma progression through increased VEGF deposition and vascular abnormalization.
miR-18a represses angiogenesis and tumor evasion by weakening vascular endothelial growth factor and transforming growth factor-β signaling to prolong the survival of glioma patients, although it is thought to be an oncogene.
Antiangiogenic strategies targeting VEGF based on tyrosine kinase inhibitors (TKIs) are currently undergoing extensive research for the treatment of glioma.Herein we demonstrated that the TKI axitinib induces DNA damage response (DDR) characterized by γ-H2AX phosphorylation and Chk1 kinase activation leading to G2/M cell cycle arrest and mitotic catastrophe in U87, T98 and U251 glioma cell lines.
Since IL-1 appears to be involved in VEGF secretion in glial tumors through an autocrine/paracrine mechanism, recombinant human IL-1-ra may evolve as a new agent for anti-angiogenic glioma therapy.
Interferon-β inhibits glioma angiogenesis through downregulation of vascular endothelial growth factor and upregulation of interferon inducible protein 10.
These results suggest that NRP1 overexpression, rather than VEGF-A or VEGFR, contributes to tumor progression and has clinical significance for glioma.
Similarly, relatively little is known about the relationship of miR-140-5p, vascular endothelial growth factor A, and matrix metalloproteinase-2 in glioma progression.
Our study also showed that HOTAIR was present in the glioma cell culture supernatant and was protected by membranes, suggesting that HOTAIR may affect glioma angiogenesis not only via regulation of VEGFA expression in the glioma cells, but also by transmission into endothelial cells via glioma cell-derived extracellular vesicles.
All glioma cell lines tested had markedly diminished production of vascular endothelial growth factor (VEGF) when cultured with rapamycin, even at doses below the IC50.
Thus, the quantity of VEGF in the glioma microenvironment seems to be crucial for the participation of microglia/macrophages on tumor progression and should be considered for developing novel therapeutic approaches.
The low expression rates of Ki-67 and VEGF in patients with grade I-II brain glioma were significantly higher than in patients with grade III-IV glioma (p<0.05).
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.