title: Human endostatin-derived synthetic peptides possess potent antiangiogenic properties in vitro and in vivo.
abstract: Pharmacological control of the angiogenic process (i.e., the neovascularization necessary for the growth and progression of tumors and metastases) is considered to be one of the most promising approaches to antineoplastic therapy. Endostatin, a 20-kDa protein derived from collagen XVIII, is one of the first recently discovered endogeneous antiangiogenic substances, but its cell targets and mechanism(s) of action are still unknown. We thought it would be interesting to test whether shorter peptides derived from endostatin might preserve its antiangiogenic activity. Four synthetic peptides corresponding to the sequences 6-49 (I), 50-92 (II), 93-133 (III), and 134-178 (IV) of human endostatin were tested for their ability to inhibit endothelial cell proliferation, migration, and both in vitro and in vivo angiogenesis. Fragment I (and fragment IV in the tests performed) was found to be fully biologically active in all of the angiogenesis assays, and sometimes showed even greater potency and efficacy than full-length human endostatin itself.
authors.affiliation: Department of Pharmacology, School of Medicine, University of Milano, Via Vanvitelli, 32, 20129 Milano, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Cattaneo
authors.forename: Sandra
authors.initials: S
authors.lastname: Pola
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Francescato
authors.forename: Francesco
authors.initials: F
authors.lastname: Chillemi
authors.forename: Lucia Maria
authors.initials: LM
authors.lastname: Vicentini
mesh_terms: D000595:Amino Acid Sequence; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen / Q000737:chemistry / Q000494:pharmacology*; D043170:Collagen Type XVIII; D043169:Endostatins; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014471:Umbilical Veins
chemical_list: D020533:Angiogenesis Inhibitors; D043170:Collagen Type XVIII; D043169:Endostatins; D010446:Peptide Fragments; D003094:Collagen