Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo

Abstract

Clinical and experimental studies suggest that angiogenesis is a prerequisite for solid tumour growth. Several growth factors with mitogenic or chemotactic activity for endothelial cells in vitro have been described, but it is not known whether these mediate tumour vascularization in vivo. Glioblastoma, the most common and most malignant brain tumour in humans, is distinguished from astrocytoma by the presence of necroses and vascular proliferations. 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. The high-affinity tyrosine kinase receptor for VEGF, flt, although not expressed in normal brain endothelium, is upregulated in tumour endothelial cells in vivo. These observations strongly support the concept that tumour angiogenesis is regulated by paracrine mechanisms and identify VEGF as a potential tumour angiogenesis factor in vivo.

Expression of RECK in endothelial cells of glioma: comparison with CD34 and VEGF expressions

“…[10][11][12][13] Among angiogenic agents, VEGF is the most studied one, and its role in driving the angiogenic process in glioma is well known. [10][11][12][13] As mentioned by the previous authors, our study also proved the correlation of VEGF expression and glioma grades. In glioblastoma group, the expression of VEGF was at least 70%.…”

“…Angiogenesis markers such as platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), transforming growth factor beta (TGF-B) and vascular endothelial growth factor (VEGF) have been mentioned to play a role in this process. [7][8][9][10][11][12][13] However, there has not been any published report explaining the angiogenesis profile of RECK in glioma. Therefore in this study, we aimed at exploring RECK role in angiogenesis of glioma by performing immunohistochemistry study and comparing it with other well-known angiogenesis markers such as CD34 and VEGF.…”

Tumour hypoxia and vascular density as predictors of metastasis in squamous cell carcinoma of the uterine cervix

“…These proteins include cell adhesion molecules, proteindegrading enzymes and positive and negative angiogenesis factors (Brown and Giaccia, 1994;Dachs and Stratford, 1996). As an example, the expression of vascular endothelial growth factor, a positive angiogenesis factor known to be involved in the angiogenesis of cervical carcinoma (Guidi et al, 1995) is up-regulated significantly under hypoxic conditions both in vitro and in vivo (Plate et al, 1992;Shweiki et al, 1992;Waleh et al, 1995;Mazure et al, 1996).…”

Sp1 recognition sites in the proximal promoter of the human vascular endothelial growth factor gene are essential for platelet-derived growth factor-induced gene expression

“…Vascular endothelial growth factor (VEGF) has been identi®ed as a key mediator of tumor angiogenesis (recently review in Martiny- Baron and Marme , 1995;Thomas, 1996). Human tumor biopsies exhibit enhanced expression of VEGF mRNAs by malignant cells and VEGF receptor mRNAs in adjacent endothelial cells (Plate et al, 1992;Weindel et al, 1994). Interference with the VEGF/VEGF receptor system either by application of anti-VEGF monoclonal antibodies to nude mice which carry VEGF-producing tumor cells, or by retrovirus-driven expression of a dominant-negative mutant of the VEGF receptor¯k-1 in tumor endothelia of such animals resulted in an almost complete inhibition of vascularization and tumor growth (Kim et al, 1993;Millauer et al, 1994).…”