Analysis of Alk-1 Signaling in Endothelial Cells and its Role in Breast Tumor Angiogenesis. Addendum

Abstract : The process of tumor angiogenesis i.e. the vascularization of the tumor mass by formation of new blood vessels is important for tumor growth and metastasis. Inhibition of tumor angiogenesis is therefore an important goal for therapeutic intervention in breast cancer. Understanding the regulation of tumor angiogenesis at the molecular level is a prerequisite for successful manipulation of this process. Angiogenesis is regulated by the coordinated action of various growth factors and their receptors among the Alk-1 a member of the TGF-beta receptor family. While convincing genetic evidence has demonstrated an essential role of Alk-1 in developmental angiogenesis and the maintenance of the vascular system in the adult the possible role of Alk-1 in tumor angiogenesis as well as its cellular and molecular functions in endothelial cells need to be investigated. To this end we have generated a variety of tools for the analysis of Alk-1 function and have made further progress in elucidating its role in the regulation of endothelial cell growth and survival. These studies have the potential of leading to the identification of novel targets in the TGF-beta signaling system for anti-angiogenic intervention in breast cancer.