[Mechanisms of cancer angiogenesis]

The early stages of tumor growth are independent of blood vessels. When a tumor reaches a volume of approximately 2 mm3, it requires an oxygen and nutrient supply, like other tissues. Satisfaction of the metabolic demands of tumor tissue occurs through neovascularization, which is also called tumor angiogenesis. The best-characterized mechanism of new vessel formation is endothelial cell sprouting. This three-step process involves dilation of a preexisting vessel and basement membrane degradation as well as endothelial cell proliferation and migration, which lead to the restoration of vessel continuity. Eventually, a new vascular basement membrane is deposited and proliferating pericytes are recruited to stabilize the newly formed vessels. Other examples of tumor neovascularization are intussusceptive and glomerular angiogenesis. Since endothelial cell recruitment, proliferation, and migration is not required, they proceed faster and at lower energetic costs. These types of angiogenesis predominate in the colon, stomach, thymus, and skin cancers as well as gliosarcomas mulitiforme. Moreover, tumors can also be fed by co-opting host vessels or by forming "pseudovessels" in angiogenesis mimicry. All the processes mentioned in this review are not mutually exclusive; on the contrary, they are closely connected in many cases.Therefore, effective anticancer therapies should not only focus on diminishing the activity of proangiogenic factors targeted during vessel sprouting, but include the great variety of vessel factors.