Mechanisms of normal and tumor-derived angiogenesis

Often those diseases most evasive totherapeutic intervention usurp the human body's own cellular machineryor deregulate normal physiological processes for propagation.Tumor-induced angiogenesis is a pathological condition that resultsfrom aberrant deployment of normal angiogenesis, an essential processin which the vascular tree is remodeled by the growth of newcapillaries from preexisting vessels. Normal angiogenesis ensures thatdeveloping or healing tissues receive an adequate supply of nutrients.Within the confines of a tumor, the availability of nutrients islimited by competition among actively proliferating cells, anddiffusion of metabolites is impeded by high interstitial pressure (Jain RK. Cancer Res 47: 3039-3051, 1987). As a result, tumorcells induce the formation of a new blood supply from the preexisting vasculature, and this affords tumor cells the ability to survive andpropagate in a hostile environment. Because both normal and tumor-induced neovascularization fulfill the essential role of satisfying the metabolic demands of a tissue, the mechanisms by whichcancer cells stimulate pathological neovascularization mimic thoseutilized by normal cells to foster physiological angiogenesis. Thisreview investigates mechanisms of tumor-induced angiogenesis. Thestrategies used by cancer cells to develop their own blood supply arediscussed in relation to those employed by normal cells duringphysiological angiogenesis. With an understanding of blood vesselgrowth in both normal and abnormal settings, we are better suited todesign effective therapeutics for cancer.