The relationship between hypoxia and angiogenesis.

Recent studies have generated a large amount of data supporting the hypothesis that hypoxia drives tumor angiogenesis. The relationship between the two is often considered a matter of supply and demand: ineffectively-vascularized tumor tissue becomes hypoxic, stimulating neoangiogenesis to improve the influx of oxygen, thereby diminishing the angiogenic drive. Although this paradigm is logically pleasing, much of what is known about tumor biology argues against such a straightforward relationship. In fact, some preclinical data convincingly shows that tumor hypoxia and angiogenesis do not always go hand in hand. It is important to begin to explore means of reconciling these discrepancies. Although poor oxygenation is a strong stimulus for tumor angiogenesis, (1) the pathogenesis of tumor hypoxia is much more complicated than the supply-demand paradigm lets on and (2) hypoxia is not necessarily sufficient or necessary for neovascularization to occur. These subtleties may help to explain why so much data disagrees with the current hypoxia-angiogenesis model and may begin to build a better understanding of the role hypoxia plays in tumor vascularization. This article will review what is known about hypoxia and angiogenesis in nononcological processes and will apply these lessons to tumor biology to more deeply describe their relationship.