The Angiogenic Switch: Implications in the Regulation of Tumor Dormancy

Angiogenesis plays an established role in the growth promotion of dormant micrometastasis, because blood vessels deliver oxygen and nutrients into the tumor microenvironment. A discrete event termed the angiogenic switch has been recognized as key in promoting the transition towards a clinically aggressive tumor. This concept generally describes a permanent change in the angiogenic capacity of the tumor sustained by genetic events occurring in cancer cells. Recent evidence, however, indicates that a transient angiogenic switch delivered by components of the tumor microenvironment can also convey tumorigenic properties to tumor cells. Why is the angiogenic switch so fundamental in the promotion of tumor growth? In addition to the recognized feeding function of blood vessels, there is accumulating evidence suggesting that endothelial cells and perhaps other cellular components of the microenvironment-communicate both positive and negative signals to tumor cells. This cross-talk between heterogeneous cell types could turn out to be important in the regulation of cancer cells' behaviour. In this review, we discuss the possible implications of the angiogenic switch on our understanding of the regulation of tumor dormancy.