TUMOR INVASION, PROTEOLYSIS, AND ANGIOGENESIS

In this review, some of the current literature on the regulation of pr oteolysis and angiogenesis during tumor invasion is discussed. Due to the critical location of brain tumors, an understanding of tumor cell interactions with the local environment is particularly relevant. Tiss ue breakdown during tumor invasion is associated with proteolytic acti vity, mediated by tumor cells, and surrounding host cells. This review covers two classes of proteinases and inhibitors that have commonly b een associated with tumor invasion i.e., plasminogen activator (PA)/pl asmin and matrix metalloproteinases (MMP) with special emphasis on the MMP inhibitors, TIMP-1 and TIMP-2. At different steps of the metastat ic process, tumor cells interact with endothelial cells. Tumor cells a lso stimulate the formation of new vessels through the expression of s pecific angiogenic molecules. At least eight angiogenic molecules have been purified, sequenced and cloned, four of which are discussed here . Regulation of angiogenic activity has been the focus of intense stud ies recently, and a wide range of synthetic and natural angiogenesis i nhibitors have been discovered. Targeting of angiogenic molecules and tumor vasculature may prove useful in future cancer therapeutic strate gies.