Inhibition of angiogenesis, tumour growth and experimental metastasis of human fibrosarcoma cells HT1080 by a multimeric form of the laminin sequence Tyr-Ile-Gly-Ser-Arg (YIGSR).
A multimeric peptide, Ac-Y16, consisting of 16 YIGSR sequences from laminin was evaluated for its effect on experimental metastasis, angiogenesis and tumour growth of HT1080 human fibrosarcoma cells. Co-injection of 0.5 mg per mouse of Ac-Y16 i.v. with HT 1080 cells inhibited lung colonisation by 100%, whereas 0.5 mg per mouse of monomeric Ac-YIGSR-NH2(AcY1) inhibited by 94%. Ac-Y16 did not show any direct cytotoxicity in tumour cells in vivo. The effect of the peptides on angiogenesis and tumour growth respectively were evaluated by counting areas of neovessels and weighing tumours after the s.c. implantation of HT1080 cells with basement membrane extracts and the peptide into nude mice. Co-injection of 0.5 mg per mouse of AC-Y16 s.c. with HT1080 cells inhibited angiogenesis and tumour growth by 92% (P<0.05) and 76% (P<0.05) respectively, whereas 0.5 mg per mouse of monomeric Ac-YIGSR-NH2(Ac-Y1) inhibited angiogenesis and tumour growth by 40% (P<0.05) and 9% (P>0.05) respectively. It can be inferred from these data that anti-tumour effects of Ac-Y16 are likely to result from anti-angiogenesis. Intraperitoneal administration of Ac-Y16 was also effective in inhibiting angiogenesis, tumour growth and lung colonisation of HT1080 cells. It was concluded that the multimeric YIGSR-containing peptide, Ac-Y16, inhibits angiogenesis, tumour growth and experimental metastasis more than the monomeric form and that it is active when administered i.p., iv. and s.c.
Iwamoto
Y
Y
Department of Orthopaedic Surgery, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Nomizu
M
M
Yamada
Y
Y
Ito
Y
Y
Tanaka
K
K
Sugioka
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002448:Cell Adhesion / Q000187:drug effects; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D006801:Humans; D007797:Laminin / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007797:Laminin; D009842:Oligopeptides; C081571:tyrosyl-isoleucyl-glycyl-seryl-arginine