Overexpression of vascular endothelial growth factor induces cell transformation in cooperation with fibroblast growth factor 2

Human Herpesvirus 8 (HHV-8)-Encoded Cytokines Induce Expression of and Autocrine Signaling by Vascular Endothelial Growth Factor (VEGF) in HHV-8-Infected Primary-Effusion Lymphoma Cell Lines and Mediate VEGF-Independent Antiapoptotic Effects

“…Findings of Aoki and Tosato (2) that VEGF-A neutralizing antibodies inhibit PEL growth, in addition to the development of lymphomatous effusions, in inoculated mice are consistent with this hypothesis. Although it is notable that no effects of VEGF-A neutralization on the growth of PEL cells in culture were found in this study, it is possible that intracellular autocrine signaling (not susceptible to blocking by neutralizing antibodies) occurs in cultured PEL cells, as appears to be the case in at least one other system (22). VEGFR-1 has been associated mainly with cell migration rather than mitogenesis, but VEGFR-1 is able to mediate mitogenic responses in at least some cell types (15,25), and VEGFR-1 is dramatically increased in rat retinal pigment epithelial cells transformed by constitutive expression of VEGF (17).…”

Anti-tumor angiogenesis therapy using soluble receptors: enhanced inhibition of tumor growth when soluble fibroblast growth factor receptor-1 is used with soluble vascular endothelial growth factor receptor

“…For example: ( a) high -level expression of FGF -2 and VEGF was well correlated with a high degree of vascularization in melanomas, 28 with the advancement of clinical stage in neuroblastomas, 29 and was associated with metastasis; 30 (b ) in microvascular endothelial cells in culture, a combination of FGF -2 and either VEGF or HGF induced further capillary -like tube formation (corresponding to angiogenesis in vivo ); 31,32 ( c) similarly, regulation of tube formation by VEGF-C has been found to depend on the presence and the concentration of FGF -2 in three endothelial cell lines; 33 (d ) FGF -2 increased the expression of VEGFR in endothelial cells, 34 and of VEGF itself in both osteoblastic cells 35 and granulomas; 21 (e ) VEGF induced an expression of FGFR1 in retinal pigment epithelial cells. 36 Furthermore, it has been suggested that VEGF and FGF -1 acted synergistically to switch the nonangiogenic phenotype to an angiogenic one in a transgenic animal model of multistage tumorigenesis in which SV40 T antigen is expressed under a rat insulin promoter ( RipTag2; Ref. [37 ]); 38,39 (f) in the quail chorioallantoic membrane, FGF -2 selectively stimulates the angiogenesis of smaller arteries, whereas VEGF dilates and increases the permeability of larger arteries; 40 (g) FGF -2 gene -disrupted mice are morphologically normal, 41,42 whereas VEGF -gene knockout mice die in utero with major angiogenic anomalies; 43 (h ) in human umbilical endothelial cells, FGF -2 is more potent at inducing cell proliferation than VEGF, but VEGF stimulates migration more effectively than FGF -2.…”

Regulation of vascular endothelial growth factor (VEGF) expression is mediated by internal initiation of translation and alternative initiation of transcription

“…Inhibition of VEGF expression, by injection of speci®c antibodies or by overexpression of dominant negative VEGF receptor mutant, resulted in a dramatic inhibitory eect on tumor growth demonstrating its pivotal role in tumor angiogenesis (Kim et al, 1993;Millauer et al, 1994). Overexpression of VEGF induces cell transformation in cooperation with Fibroblast Growth Factor 2 (FGF2) (Guerrin et al, 1997). In addition, targeted inactivation of the VEGF gene resulted in heterozygous embryonic lethality which clearly demonstrates its necessity during embryonal development (Ferrara et al, 1996).…”