Human endostatin-derived synthetic peptides possess potent antiangiogenic properties in vitro and in vivo.
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.
Cattaneo
Maria Grazia
MG
Department of Pharmacology, School of Medicine, University of Milano, Via Vanvitelli, 32, 20129 Milano, Italy.
Pola
Sandra
S
Francescato
Pierangelo
P
Chillemi
Francesco
F
Vicentini
Lucia Maria
LM
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
D020533:Angiogenesis Inhibitors; D043170:Collagen Type XVIII; D043169:Endostatins; D010446:Peptide Fragments; D003094:Collagen