an ip-10 (cxcl10)-derived peptide inhibits angiogenesisip-10(cxcl10)衍生肽抑制血管生成.pdfVIP

An IP-10 (CXCL10)-Derived Peptide Inhibits Angiogenesis 1,2,3 3 1 1,2,3 2,3 Cecelia C. Yates-Binder *, Margaret Rodgers , Jesse Jaynes , Alan Wells , Richard J. Bodnar *, Timothy Turner1 1Tuskegee University, Center for Cancer Research, Tuskegee, Alabama, United States of America, 2 Departments of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America, 3 Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, United States of America Abstract Angiogenesis plays a critical role in processes such as organ development, wound healing, and tumor growth. It requires well-orchestrated integration of soluble and matrix factors and timely recognition of such signals to regulate this process. Previous work has shown that newly forming vessels express the chemokine receptor CXC receptor 3 (CXCR3) and, activation by its ligand IP-10 (CXCL10), both inhibits development of new vasculature and causes regression of newly formed vessels. To identify and develop new therapeutic agents to limit or reverse pathological angiogenesis, we identified a 21 amino acid fragment of IP-10, spanning the a-helical domain residues 77–98, that mimic the actions of the whole IP-10 molecule on endothelial cells. Treatment of the endothelial cells with the 22 amino acid fragment referred to as IP-10p significantly inhibited VEGF-induced endothelial motility and tube formation in vitro, properties critical for angiogenesis. Using a Matrigel plug assay in vivo, we demonstrate that IP-10p both prevented vessel formation and induced involution of nascent vessels. CXCR3 neutralizing antibody was ab