Steps toward mapping the human vasculature by phage display
Nature Medicine
February 2002 Volume 8 Number 2 pp 121 - 127
Wadih Arap1, 2, Mikhail G. Kolonin1, 11, Martin Trepel1, 11, Johanna Lahdenranta1, Marina Cardó-Vila1, Ricardo J. Giordano1, Paul J. Mintz1, Peter U. Ardelt1, Virginia J. Yao1, Claudia I. Vidal1, Limor Chen1, Anne Flamm3, Heli Valtanen9, Lisa M. Weavind5, Marshall E. Hicks6, Raphael E. Pollock7, Gregory H. Botz5, Corazon D. Bucana2, Erkki Koivunen9, Dolores Cahill10, Patricia Troncoso8, Keith A. Baggerly4, Rebecca D. Pentz3, Kim-Anh Do4, Christopher J. Logothetis1 & Renata Pasqualini1, 2
The molecular diversity of receptors in human blood vessels remains largely unexplored. We developed a selection method in which peptides that home to specific vascular beds are identified after administration of a peptide library. Here we report the first in vivo screening of a peptide library in a patient. We surveyed 47,160 motifs that localized to different organs. This large-scale screening indicates that the tissue distribution of circulating peptides is nonrandom. High-throughput analysis of the motifs revealed similarities to ligands for differentially expressed cell-surface proteins, and a candidate ligand–receptor pair was validated. These data represent a step toward the construction of a molecular map of human vasculature and may have broad implications for the development of targeted therapies.
1. Department of Genito-Urinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
2. Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
3. Department of Clinical Ethics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
4. Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
5. Department of Critical Care, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
6. Department of Diagnostic Radiology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
7. Department of Surgical Oncology and The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
8. Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
9. Department of Biosciences, Division of Biochemistry, University of Helsinki, Helsinki, Finland
10. Max Planck Institute of Molecular Genetics, Berlin, Germany
11. M.G.K. and M.T. contributed equally to this study. |
