Pathways for aberrant angiogenesis in pancreatic cancer

Abstract

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease. Althoughthe specific mechanisms that dictate its biological aggressiveness are notclearly established, it is characterized by a variety of molecularalterations as well as by the overexpression of mitogenic and angiogenicgrowth factors and their receptors. PDACs also express high levels ofvascular endothelial growth factor (VEGF). Recent studies indicate thatsuppression of VEGF expression attenuates pancreatic cancer celltumorigenicity in a nude mouse model, and that VEGF can exert directmitogenic effects on some pancreatic cancer cells. These findings suggestthat cancer cell derived VEGF promotes pancreatic cancer growth in vivo viaa paracrine angiogenic pathway and an autocrine mitogenic pathway, andprovide novel opportunities for therapeutic intervention in this deadlydisease.