Vessel co-option:: How tumors obtain blood supply in the absence of sprouting angiogenesis

The hypothesis that solid tumors are dependent on angiogenesis, the formation of new vessels, for outgrowth and metastasis has acquired a central position in cancer research and has since inspired many scientists for several decades. Among the various angiogenic stimuli that are secreted by tumor cells, members of the Vascular Endothelial Growth Factor (VEGF) family are most prominent. More recently it has become clear, however, that tumors may use alternative ways to obtain blood supply. Vessel co-option, the use of pre-existent vessels, was described first in the brain, one of the most densely vascularized organs in the body. Thus, brain tumors may develop without the need of an angiogenic switch to occur. Obviously, this way of blood supply will not be affected by angiogenesis inhibition. In addition, it is predicted that tumors with this type of behavior will be less visible in contrast-enhanced MRI. In this article we present our recently developed mouse brain model of vessel co-option in melanoma. The effects of expression of VEGF on tumor vascularity, and on MRI visualization of these brain lesions are described. Possible consequences of anti-angiogenesis therapy are discussed.