Recombinant human VEGF165b protein is an effective anti-cancer agent in mice

Abstract

Tumour growth is dependent on angiogenesis, the key mediator of which is vascular endothelial growth factor-A (VEGF-A). VEGF-A exists as two families of alternatively spliced isoforms - pro-angiogenic VEGF(xxx) generated by proximal, and anti-angiogenic VEGF(xxx)b by distal splicing of exon 8. VEGF(165)b inhibits angiogenesis and is downregulated in tumours. Here, we show for the first time that administration of recombinant human VEGF(165)b inhibits colon carcinoma tumour growth and tumour vessel density in nude mice, with a terminal plasma half-life of 6.2h and directly inhibited angiogenic parameters (endothelial sprouting, orientation and structure formation) in vitro. Intravenous injection of (125)I-VEGF(165)b demonstrated significant tumour uptake lasting at least 24h. No adverse effects on liver function or haemodynamics were observed. These results indicate that injected VEGF(165)b was taken up into the tumour as an effective anti-angiogenic cancer therapy, and provide proof of principle for the development of this anti-angiogenic growth factor splice isoform as a novel cancer therapy.

Overexpression of VEGF165b in Podocytes Reduces Glomerular Permeability

“…13,19,45,46 Thus, parenterally administered rhVEGF 165 b (intraperitoneal and subcutaneous) halts colonic carcinoma tumor growth in nude mice. 17 We have also shown that transgenic mice overexpressing VEGF 165 b in mammary tissue have inhibited physiologic angiogenesis. 15 VEGF 165 b inhibits both angiogenesis and vasodilatation through inhibition of VEGF 165 -mediated full activation of VEGF-R2.…”

“…Replacement of 8a by exon 8b in the VEGF xxx b family produces peptides that are antiangiogenic, inhibit permeability chronically, and reduce rather than promote tumor growth. 13, [15][16][17][18][19][20] Alternative splicing of ex- The gDNA is digested with EcoRI, and a probe made from the cDNA is used to generate the transgene. There was a single EcoRI site in the 5Ј end of the insert, so multiple insertions should generate multiple different-sized bands in the transgene.…”

Vascular endothelial growth factor-A165b prevents diabetic neuropathic pain and sensory neuronal degeneration

“…This twice weekly i.p. dosing regime has proven successful in the amelioration of diabetic nephropathy [21], traumatic nerve injury [16] and in vivo tumour models [22]. .…”

Vascular Endothelial Growth Factor-A165b Is Protective and Restores Endothelial Glycocalyx in Diabetic Nephropathy

“…21 We therefore assessed the efficacy of systemic rh VEGF-A 165 b injections in STZ-induced diabetes in DBA2J mice before and after the onset of diabetic nephropathy ( Figure 4A). After 2 weeks of consistent hyperglycemia, lowdose 0.04mg/g rh VEGF-A 165 b injections were initiated and continued until an approved study endpoint occurred (significant weight loss).…”