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 beta 1 chain sequence has an inhibi tory effect on tumour growth and the metastasis of melanoma and fibrosarcom a cells. In the present study, we investigated whether the multimeric YIGSR peptide (Ac-Y16) has an antiproliferative effect and/or prevents the metas tasis of human pre-B acute lymphoblastic leukaemia cells (NALM6) in severe combined immune deficient (SCID) mice. In in vitro studies, Ac-Y16 signific antly inhibited leukaemic cell colony formation and the invasion of NALM6 c ells in a Matrigel-based assay. The tumour growth and leukaemic infiltratio n 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 su bcutaneous tumours was significantly suppressed by Ac-Y16 in a dose-depende nt manner. Flow cytometry analysis showed that the leukaemic infiltration w as significantly inhibited in ail organs with 1.5-2.0 mg of Ac-Y16. Leukaem ic infiltrations in the brain were inhibited with 0.5 mg of Ac-Y16, and tho se in brain and bane marrow were also inhibited with 1.0 mg of Ac-Y16. With Ac-S16, a control;scrambled peptide; the only significant inhibition of th e leukaemic infiltration was observed in bone marrow at a much higher dose. These data suggest that the multimeric YIGSR peptide can inhibit the tumou r growth and metastasis of leukaemic cells and may be useful as a potential therapeutic reagent for leukaemic infiltrations.