Specific antagonists have been successfully developed for several different
integrins. Clinical trials have been initiated to study
therapeutic uses of these inhibitors in
cancer,
thrombosis, and inflammatory diseases. Most efforts to date have focused on the platelet
integrin alphaIIbbeta3, endothelial alphavbeta3, and the leukocyte
integrin alpha4beta1. However, the
integrin family contains additional members with interesting tissue specificities and functional properties that could also be useful molecular targets for disease intervention. In many cases, specific recognition motifs for these
integrins have not been identified, which has precluded development of specific antagonists. Our recent studies of thrombospondin-1 and thrombospondin-2 recognition by
integrins have revealed novel motifs for alpha3beta1 and alpha6beta1
integrins as well as new motifs recognized by the well studied
alpha4beta1 integrin. These three
integrins play distinct roles in angiogenesis and its modulation by
thrombospondins. This review will discuss recent insights into the specificities of alpha3beta1 and alpha6beta1
integrins, their functions in angiogenesis, and potential applications for antagonists of these
integrins and of alpha4beta1 to control
pathological angiogenesis and other diseases.