Effect of HGF-like basic hexapeptides on angiogenesis.
The interaction of glycosaminoglycans (GAG) with peptides relies on noncovalent binding to basic amino acid sequences, for which a minimal requirement is a pentapeptide region in the protein and the sulfated and carboxyl region in the GAG. Since such sequences are present in the heparin-binding angiogenic cytokines, including hepatocyte growth factor (HGF), we have postulated that such small peptides may have biological activity. Two basic peptide regions of the beta chain of HGF (RYRNKH512-516, HHRGK645-649) exhibited significant antiangiogenic activity in vivo in the chorioallantoic membrane assay and showed some antiproliferative activity in vitro on normal human brain microvessel endothelial-but not on anchorage-independent endothelial-cells (Kaposi sarcoma). Basic HIV-TAT peptides and scrambled hexapeptides did not show similar activity, except for KRKRKR, indicating sequence specificity of the phenomena. An HGF-derived basic peptide, HHRGK, modulated tumor-induced angiogenesis in vivo by interfering with the morphogenic, but not with the proliferative, phase of the process. These observations suggest small basic peptides as a new class of angiogenesis modulators.
Fazekas
K
K
Department of Tumor Progression, National Institute of Oncology, Budapest, H-1122, Hungary.
Janovics
A
A
Döme
B
B
Koska
P
P
Albini
A
A
Tímár
J
J
D000482:Allantois / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000166:cytology; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002642:Chick Embryo; D002823:Chorion / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006493:Heparin / Q000737:chemistry; D017228:Hepatocyte Growth Factor / Q000737:chemistry*; D051379:Mice; D016513:Mice, SCID; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D014407:Tumor Cells, Cultured
D016207:Cytokines; D010455:Peptides; D017228:Hepatocyte Growth Factor; D006493:Heparin