Cellular and molecular mechanisms of nicotine's pro-angiogenesis activity and its potential impact on cancer

The present study examined the mechanisms of nicotine's effect on angiogenesis and its impact on tumor growth. Nicotine demonstrated significant (P<0.01) stimulation of the release of endothelial cell growth factor, basic fibroblast growth factor (b-FGF) but not vascular endothelial growth factor (VEGF). In a concentration-dependent manner, nicotine induced endothelial cell tube formation. Additionally, in the chick chorioallantoic membrane (CAM) model of angiogenesis, nicotine effectively induced the generation of new blood vessels (P<0.01), an effect that is mediated via b-FGF. The pro-angiogenesis effect of nicotine in the CAM model was maximally blocked by either anti-integrin alphavbeta3 or inhibitor of mitogen activated protein kinase (MAPK, ERK 1/2). In the CAM tumor implant model, nicotine doubled (P<0.01) the growth rate of breast, colon, and lung cancer. These data indicated that the pro-angiogenesis effect is mediated via b-FGF and induced through the nicotinic receptor, alphavbeta3 integrin, and MAPK.