Suppression of tumor growth by novel peptides homing to tumor-derived new blood vessels.
Novel peptides homing to angiogenic vessels were recently isolated from a phage-displayed random pentadecapeptide library. One of the isolated peptides, ASSSYPLIHWRPWAR, significantly suppressed the migration of VEGF-stimulated human umbilical vein endothelial cells. Dendoric ASSSYPLIHWRPWAR-peptide suppressed the formation of new blood vessels in dorsal air sac model mice. Furthermore, ASSSYPLIHWRPWAR-peptide and the fragment peptides containing WRP, which is revealed to be an epitope sequence, significantly suppressed the tumor growth, although 15-mer shuffled peptide derived from ASSSYPLIHWRPWAR and pentapeptides with alanine substitution of each residue of WRP did not. Taken together, ASSSYPLIHWRPWAR-peptide may cause tumor dormancy through inhibition of angiogenesis, and the WRP sequence may be the minimal and essential sequence for this activity.
Asai
Tomohiro
T
Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Nagatsuka
Mayumi
M
Kuromi
Koichi
K
Yamakawa
Satoru
S
Kurohane
Kohta
K
Ogino
Koichi
K
Tanaka
Michinori
M
Taki
Takao
T
Oku
Naoto
N
D000595:Amino Acid Sequence; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D000939:Epitopes; D006801:Humans; D007279:Injections, Subcutaneous; D008222:Lymphokines / Q000494:pharmacology; D008546:Melanoma, Experimental / Q000098:blood supply / Q000188:drug therapy*; D051379:Mice; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D019151:Peptide Library; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D012513:Sarcoma, Experimental / Q000098:blood supply / Q000188:drug therapy*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D016228:Endothelial Growth Factors; D000939:Epitopes; D008222:Lymphokines; D010446:Peptide Fragments; D019151:Peptide Library; D010455:Peptides; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors