Angiogenesis: a balancing act between integrin activation and inhibition?

Abstract

Acquisition of new genes encoding for extracellular matrix (ECM) proteins and their cognate integrin adhesive receptors, as well as secreted pro- and anti-angiogenic factors, proved to be essential for the development of functional vascular networks in the vertebrate embryo. There is now clear evidence that post-natal, pathological tissue neo-vascularization is crucial for cancer growth and therapy as well. Integrins are major ECM receptors that can exist in different functional states with respect to their affinity for ECM proteins. Regulation of integrin activation is crucial for their biological functions. In the embryo, the development of a properly patterned network of blood vessels relies upon the fine modulation of integrin activation by chemoattractant and chemorepulsive cues, such as angiogenic growth factors and semaphorins. Such a fine-tuning of endothelial integrin function is likely to be disrupted in cancer. Here, the vasculature is structurally and functionally abnormal and therefore inadequate for an efficient drug and oxygen delivery, which is a mandatory pre-requisite for successful chemotherapy and radiotherapy. It is thus important to identify the molecular mechanisms that regulate integrin function in normal ECs and which are altered in tumor ECs.