ABSTRACT
Cancer progression requires consecutive transformation events through which tumor cells escape proliferative checkpoint controls and regulatory cues from the extracellular milieu. In this process, tumor cells also acquire the ability to shape the tumor microenvironment for their survival advantage. Virtually, all clinically relevant carcinomas have undergone
the “angiogenic switch” (1), i.e., developed mechanisms to sustain an appropriate blood supply for further tumor expansion. In principle, tumor cells utilize the same programs of angiogenesis that restore organ function after ischemic, mechanical, or microbial injury. Whereas regenerative angiogenesis typically progresses to restore a functional, organ-specifi c hierarchical vascular bed, tumor vessels retain various degrees of immaturity and tortuous architecture. Thus, tumor vessels have inconsistent directions of fl ow, imperfect vessel wall architecture including abnormal pericyte recruitment, and-most importantly for the current review-increased permeability and extravasation of blood plasma components.
