The laminin-derived peptide YIGSR (Tyr-Ile-Gly-Ser-Arg) inhibits human pre-B leukaemic cell growth and dissemination to organs in SCID mice.
The YIGSR (Tyr-Ile-Gly-Ser-Arg) laminin beta1 chain sequence has an inhibitory effect on tumour growth and the metastasis of melanoma and fibrosarcoma cells. In the present study, we investigated whether the multimeric YIGSR peptide (Ac-Y16) has an antiproliferative effect and/or prevents the metastasis of human pre-B acute lymphoblastic leukaemia cells (NALM6) in severe combined immune deficient (SCID) mice. In in vitro studies, Ac-Y16 significantly inhibited leukaemic cell colony formation and the invasion of NALM6 cells in a Matrigel-based assay. The tumour growth and leukaemic infiltration in peripheral tissues were also analysed in SCID mice 9 weeks after NALM6, Matrigel and Ac-Y16 were subcutaneously co-injected. The weight of the subcutaneous tumours was significantly suppressed by Ac-Y16 in a dose-dependent manner. Flow cytometry analysis showed that the leukaemic infiltration was significantly inhibited in all organs with 1.5-2.0 mg of Ac-Y16. Leukaemic infiltrations in the brain were inhibited with 0.5 mg of Ac-Y16, and those in brain and bone marrow were also inhibited with 1.0 mg of Ac-Y16. With Ac-S16, a control-scrambled peptide, the only significant inhibition of the leukaemic infiltration was observed in bone marrow at a much higher dose. These data suggest that the multimeric YIGSR peptide can inhibit the tumour growth and metastasis of leukaemic cells and may be useful as a potential therapeutic reagent for leukaemic infiltrations.
Yoshida
N
N
Department of Pediatrics, Saga Medical School, Japan.
Ishii
E
E
Nomizu
M
M
Yamada
Y
Y
Mohri
S
S
Kinukawa
N
N
Matsuzaki
A
A
Oshima
K
K
Hara
T
T
Miyazaki
S
S
D000199:Actins / Q000235:genetics; D000818:Animals; D018941:Antigens, CD19 / Q000032:analysis; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D007797:Laminin; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009362:Neoplasm Metastasis; D015260:Neprilysin / Q000032:analysis; D009842:Oligopeptides / Q000627:therapeutic use / Q000633:toxicity*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000199:Actins; D018941:Antigens, CD19; D000970:Antineoplastic Agents; D007797:Laminin; D009842:Oligopeptides; C081571:tyrosyl-isoleucyl-glycyl-seryl-arginine; D015260:Neprilysin