Identification of a rhabdomyosarcoma targeting peptide by phage display with sequence similarities to the tumour lymphatic-homing peptide LyP-1.
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. To improve existing therapies and broaden the spectrum of cytotoxic agents that can be used in RMS treatment, we performed a phage-display-based screening for peptides that bind specifically to RMS cells. Two peptides binding to RMS and to other tumour cell lines, but not to normal skeletal muscle cells and fibroblasts, were isolated from phage-displayed random peptide libraries. One peptide, named RMS-I (CQQSNRGDRKRC) contained the integrin-binding motif RGD and its binding was blocked by an antibody against alpha(v)beta(3)integrin, which is expressed on the RMS cell line RD. The isolation of RMS-I confirmed the validity of our screening procedure. The second peptide, named RMS-II (CMGNKRSAKRPC), shows sequence similarity to a previously identified peptide with tumour lymphatic specificity, LyP-1. However, RMS-II binds in vivo to RMS xenografts better than LyP-1 and homes to the tumour blood and not to lymphatic vessels. Therefore, RMS-II represents a promising peptide for the development of RMS-specific targeting approaches.
Witt
Hendrik
H
Department of Oncology, University Children's Hospital Zurich, Zurich, Switzerland.
Hajdin
Katarina
K
Iljin
Kristina
K
Greiner
Oliver
O
Niggli
Felix K
FK
Schäfer
Beat W
BW
Bernasconi
Michele
M
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005354:Fibrosarcoma / Q000378:metabolism; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008208:Lymphatic System / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019151:Peptide Library; D010456:Peptides, Cyclic / Q000737:chemistry*; D012208:Rhabdomyosarcoma / Q000378:metabolism*; D014183:Transplantation, Heterologous
D039302:Integrin alphaVbeta3; C461500:LyP-1 protein, mouse; D009842:Oligopeptides; D010446:Peptide Fragments; D019151:Peptide Library; D010456:Peptides, Cyclic; C047981:arginyl-glycyl-aspartic acid