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

Fernanda I. Staquicini, Marina Cardó-Vila, Mikhail G. Kolonin, Martin Trepel, Julianna K. Edwards, Diana N. Nunes, Anna Sergeeva, Eleni Efstathiou, Jessica Sun, Nalvo F. Almeida, Shi Ming Tu, Gregory H. Botz, Michael J. Wallace, David J. O'Connell, Stan Krajewski, Jeffrey E. Gershenwald, Jeffrey J. Molldrem, Anne L. Flamm, Erkki Koivunen, Rebecca D. PentzEmmanuel Dias-Neto, João C. Setubal, Dolores J. Cahill, Patricia Troncoso, Kim Ahn Do, Christopher J. Logothetis, Richard L. Sidman, Renata Pasqualini, Wadih Arap

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

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 × 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.

Original languageEnglish (US)
Pages (from-to)18637-18642
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number46
DOIs
StatePublished - Nov 15 2011
Externally publishedYes

Keywords

  • Angiogenesis
  • Human disease
  • Obesity
  • Phage display
  • Tumor

ASJC Scopus subject areas

  • General

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