Inhibition at the expression of VEGF RNA and protein levels was observed in glioblastoma-astrocytoma U-87 MG cells treated with exosome-delivered siRNAs.
Additionally, proliferation, invasion, and migration assays of astrocytoma cell lines were conducted to evaluate the effects of short interfering RNA (siRNA) on these processes; in addition, these cells were subjected to western blotting to detect the expression levels of Fli-1, Ki-67, VEGF, and Cyclin D1.
In astrocytoma cell lines, cells stably overexpressing full-length ALK showed an increase in expression of pStat3 and pAkt proteins, as well as hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor-A (VEGF-A) mRNAs, in contrast to cells with knockdown of endogenous ALK which showed decreased expression of these molecules.
These tumors exhibit a high degree of vascularization, and malignant progression from astrocytoma to glioblastoma is often accompanied by increased angiogenesis and the upregulation of vascular endothelial growth factor and its receptors.
Glioblastoma multiforme expressed higher levels of Angl, but not to the same degree as pseudopalisading astrocytoma cells around necrotic and hypoxic zones expressed VEGF, as shown in previous studies.
In our study, the expression pattern of Npn-1 and VEGF by human astrocytoma cell lines and specimens was closely correlated and associated with malignant astrocytomas.
Astrocytoma cells that were transfected to express the dominant inhibitory mutant H-Ras(N17) demonstrated a reduction in VEGF secretion under both normoxic and hypoxic conditions.
This data supports the assertion that angiogenetic factor such as bFGF and VEGF may contribute to progressive change of astrocytoma by tumor angiogenesis.
Here we show that expression of an endothelial cell-specific mitogen, vascular endothelial growth factor (VEGF), is induced in astrocytoma cells but is dramatically upregulated in two apparently different subsets of glioblastoma cells.