Vascular ligand-receptor mapping by direct combinatorial selection in cancer patients

Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):18637-42. doi: 10.1073/pnas.1114503108. Epub 2011 Nov 2.


Molecules differentially expressed in blood vessels among organs or between damaged and normal tissues, are attractive therapy targets; however, their identification within the human vasculature is challenging. Here we screened a peptide library in cancer patients to uncover ligand-receptors common or specific to certain vascular beds. Surveying ~2.35 x 10(6) motifs recovered from biopsies yielded a nonrandom distribution, indicating that systemic tissue targeting is feasible. High-throughput analysis by similarity search, protein arrays, and affinity chromatography revealed four native ligand-receptors, three of which were previously unrecognized. Two are shared among multiple tissues (integrin α4/annexin A4 and cathepsin B/apolipoprotein E3) and the other two have a restricted and specific distribution in normal tissue (prohibitin/annexin A2 in white adipose tissue) or cancer (RAGE/leukocyte proteinase-3 in bone metastases). These findings provide vascular molecular markers for biotechnology and medical applications.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Annexin A4 / biosynthesis
  • Apolipoprotein E3 / biosynthesis
  • Biopsy
  • Blood Vessels / metabolism*
  • Bone Marrow / metabolism*
  • Cathepsin B / biosynthesis
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Integrin alpha4 / biosynthesis
  • Ligands
  • Neoplasms / metabolism*
  • Neovascularization, Pathologic
  • Obesity / metabolism
  • Peptide Library


  • Annexin A4
  • Apolipoprotein E3
  • Ligands
  • Peptide Library
  • Integrin alpha4
  • Cathepsin B