Microenvironmental influence on macrophage regulation of angiogenesis in wounds and malignant tumors

Angiogenesis is the development of blood vessels from an existing vasculatu re. This process is fundamental to both physiological wound healing and the growth of malignant tumors, as it restores or creates a blood supply to gr owing tissue. In both cases, the release of angiogenic molecules by macroph ages recruited to the wound or tumor site is central to the formation of th ese neovessels. Reduced vascular perfusion in tissues generates tissue isch emia and a marked reduction in local levels of oxygen (hypoxia) and glucose . Cells adapt by switching to anaerobic metabolic pathways, with a concomit ant increase in lactate production and reduction in extracellular pH. In tu mors, these microenvironmental "stress" factors stimulate tumor cells to se crete a Aide array of proangiogenic cytokines and enzymes, promoting the re -establishment of a local vascular supply. Here we review the evidence that these stress factors, in particular hypoxia and high lactate levels, stimu late macrophages to perform similar proangiogenic functions in both tumors and wounds. The resolution of wounds results in restoration of tissue integ rity and perfusion, and macrophage presence is reduced to preinjury levels. However, in tumors a high number of macrophages persists and might contrib ute to the ongoing growth, neovascularization, and metastasis of malignant cells.