1. ¹Microvascular Research Laboratories, Department of Physiology and Pharmacology, School of Veterinary Science, University of Bristol, Southwell Street, Bristol BS2 8EJ, UK
2. ²Division of Pediatrics Research, Unit 87, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, USA
3. ³Radboud University Nijmegen Medical Centre, Department of Pathology, Nijmegen, The Netherlands
4. ⁴Bristol Urological Institute, Southmead Hospital, Westbury-on-Trym, Bristol, UK

Correspondence: Dr DO Bates, Microvascular Research Laboratories, Department of Physiology and Pharmacology, School of Veterinary Science, University of Bristol, Southwell Street, Bristol BS2 8EJ, UK. E-mail: Dave.Bates@bris.ac.uk

Revised 31 January 2008; Accepted 20 February 2008; Published online 18 March 2008.

Abstract

Vascular endothelial growth factor-A is widely regarded as the principal stimulator of angiogenesis required for tumour growth. VEGF is generated as multiple isoforms of two families, the pro-angiogenic family generated by proximal splice site selection in the terminal exon, termed VEGF_xxx, and the anti-angiogenic family formed by distal splice site selection in the terminal exon, termed VEGF_xxxb, where xxx is the amino acid number. The most studied isoforms, VEGF₁₆₅ and VEGF₁₆₅b have been shown to be present in tumour and normal tissues respectively. VEGF₁₆₅b has been shown to inhibit VEGF- and hypoxia-induced angiogenesis, and VEGF-induced cell migration and proliferation in vitro. Here we show that overexpression of VEGF₁₆₅b by tumour cells inhibits the growth of prostate carcinoma, Ewing's sarcoma and renal cell carcinoma in xenografted mouse tumour models. Moreover, VEGF₁₆₅b overexpression inhibited tumour cell-mediated migration and proliferation of endothelial cells. These data show that overexpression of VEGF₁₆₅b can inhibit growth of multiple tumour types in vivo indicating that VEGF₁₆₅b has potential as an anti-angiogenic, anti-tumour strategy in a number of different tumour types, either by control of VEGF₁₆₅b expression by regulation of splicing, overexpression of VEGF₁₆₅b, or therapeutic delivery of VEGF₁₆₅b to tumours.