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

E S Rennel, M A Hamdollah-Zadeh, E R Wheatley, A Magnussen, Y Schuler, S P Kelly, C Finucane, D Ellison, S Cebe-Suarez, K Ballmer-Hofer, S Mather, L Stewart, DO Bates, SJ Harper

Research output: Contribution to journalArticle (Academic Journal)peer-review

75 Citations (Scopus)

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.
Translated title of the contributionRecombinant human VEGF165b protein is an effective anti-cancer agent in mice
Original languageEnglish
Pages (from-to)1883 - 1894
Number of pages11
JournalEur J Cancer
Volume44
DOIs
Publication statusPublished - Sep 2008

Fingerprint Dive into the research topics of 'Recombinant human VEGF165b protein is an effective anti-cancer agent in mice'. Together they form a unique fingerprint.

Cite this