Search

Neovascularisation is critical for supporting the rapid growth of solid tumours (Folkman, 1990). Tumour angiogenesis appears to be achieved by the overexpression of angiogenic agents within solid tumours that stimulate host vascular endothelial cell mitogenesis and possibly chemotaxis. It is well established now that the induction of vascular endothelial growth factor (VEGF) expression, including via tumour hypoxia (Hlatky et al, 1994), plays a major role in tumour angiogenesis (Dvorak et al, 1991; Millauer et al, 1994; Goldman et al, 1998). In recent years, it has been widely shown that VEGF activity is a key feature during tumour growth and angiogenesis, and that blocking of this signal transduction pathway may inhibit tumour progression (Cheng et al, 1996; Relf et al, 1997). In vivo, VEGFs act as potent mitogenic factors for endothelial cells and as blood vessel permeabilising agents (Senger et al, 1983; Plouet et al, 1989; Klagsbrun and Soker, 1993; Yuan et al, 1996). The VEGF gene family currently includes six members: VEGF-A (prototype VEGF), placenta growth factor (PlGF), VEGF-B, VEGF-C, VEGF-D and VEGF-E, (produced by Orf virus), (reviewed by Veikkola et al, 2000). VEGF is a homodimeric glycoprotein that exists in six isoforms containing 121, 145, 162, 165, 189 and 206 amino-acid residues as a result of alternative splicing from a single gene (Ferrara and Davis-Smith, 1997; Lange et al, 2003). The predominant and the best characterised VEGF species is the heparin-binding 165-amino acid-long form VEGF165 (reviewed by Neufeld et al, 1999).