Identification of a rhabdomyosarcoma targeting peptide by phage display with sequence similarities to the tumour lymphatic-homing peptide LyP-1

Authors

  • Hendrik Witt,

    1. Department of Oncology, University Children's Hospital Zurich, Zurich, Switzerland
    Current affiliation:
    1. Department of Paediatric Oncology, Haematology and Immunology, University of Heidelberg, Heidelberg, Germany
    Search for more papers by this author
    • The first two authors contributed equally to this work.

  • Katarina Hajdin,

    1. Department of Oncology, University Children's Hospital Zurich, Zurich, Switzerland
    Search for more papers by this author
    • The first two authors contributed equally to this work.

  • Kristina Iljin,

    1. Department of Oncology, University Children's Hospital Zurich, Zurich, Switzerland
    Current affiliation:
    1. Medical Biotechnology, VTT Technical Research Centre of Finland, Turku, Finland
    Search for more papers by this author
  • Oliver Greiner,

    1. Department of Oncology, University Children's Hospital Zurich, Zurich, Switzerland
    Search for more papers by this author
  • Felix K. Niggli,

    1. Department of Oncology, University Children's Hospital Zurich, Zurich, Switzerland
    Search for more papers by this author
  • Beat W. Schäfer,

    1. Department of Oncology, University Children's Hospital Zurich, Zurich, Switzerland
    Search for more papers by this author
  • Michele Bernasconi

    Corresponding author
    1. Department of Oncology, University Children's Hospital Zurich, Zurich, Switzerland
    2. Experimental Infectious Diseases and Cancer Research, University Children's Hospital Zurich, Zurich, Switzerland
    • Experimental Infectious Diseases and Cancer Research, University Children's Hospital of Zurich, August Forel Strasse 1, CH-8008 Zurich, Switzerland
    Search for more papers by this author
    • Fax: +41-44 634-88-59.


Abstract

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 αvβ3integrin, 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. © 2008 Wiley-Liss, Inc.

Ancillary