Recent developments in the regulation of the angiogenic switch by cellular stress factors in tumors

Angiogenesis in tumors is controlled by the so-called 'angiogenic switch' which allows the passage from low invasive and poorly vascularized tumors to highly invasive and angiogenic tumors. A number of cellular stress factors such as hypoxia, nutrient deprivation or inducers of reactive oxygen species (ROS) are important stimuli of angiogenic signalling. The HIF system plays a significant role in several of these effects and the molecular mechanisms of its regulation have recently been characterized. In addition, HIF-independent mechanisms have been described which involved number of other molecules and transcription factors such as nuclear factor-(kappa)B (NF-(kappa)B) and p53. p53 is an important intracellular mediator of the stress response and is now also recognized as a modifier of the angiogenic response. p53 may interact with the HIF system but may also have direct effects on angiogenesis regulators or interfere with translation mechanisms of angiogenesis factors.