Vascular endothelial growth factor. From basic research to clinical application

There is increasing evidence to support the concept that growth and metastasis of solid tumors, including those of gastrointestinal tract, is facilitated by neoangiogenesis. Vascular Endothelial Growth Factor (VEGF) is one of the most powerful known inducer of endothelial cell growth. Therefore, VEGF is likely to contribute to tumor growth by promoting angiogenesis and stroma formation both directly, through its neovascularization inducing activity, and indirectly, by increasing vascular permeability. In addition, VEGF facilitates tumor diffusion favouring metastatic spread of cancer cells. In view of these implications, it is important to understand the physiopathological role played by this factor. In this review the authors present the accumulating body of data on the biological and functional properties of VEGF, paying special reference to new evidence on its contribution in tumor immune escape, through a marked inhibition of differentiation and activity of the professional antigen presenting cells (APC), namely dendritic cells (DC). As the molecular and cellular events that underlie the functional role of VEGF in tumor angiogenesis and immune suppression become better defined, rational pharmacological and/or gene therapies can be derived in order to treat those neoplasms, such as pancreatic adenocarcinoma, not well amenable to chemo- and radiotherapy or immunotherapy.