Ligand-directed surface profiling of human cancer cells with combinatorial peptide libraries

Mikhail G. Kolonin, Laura Bover, Jessica Sun, Amado J. Zurita, Kim Anh Do, Johanna Lahdenranta, Marina Cardó-Vila, Ricardo J. Giordano, Diana E. Jaalouk, Michael G. Ozawa, Catherine A. Moya, Glauco R. Souza, Fernanda I. Staquicini, Akihiko Kunyiasu, Dominic A. Scudiero, Susan L. Holbeck, Edward A. Sausville, Wadih Arap, Renata Pasqualini

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

A collection of 60 cell lines derived from human tumors (NCI-60) has been widely explored as a tool for anticancer drug discovery. Here, we profiled the cell surface of the NCI-60 by high-throughput screening of a phage-displayed random peptide library and classified the cell lines according to the binding selectivity of 26,031 recovered tripeptide motifs. By analyzing selected cell-homing peptide motifs and their NCI-60 recognition patterns, we established that some of these motifs (a) are similar to domains of human proteins known as ligands for tumor cell receptors and (b) segregate among the NCI-60 in a pattern correlating with expression profiles of the corresponding receptors. We biochemically validated some of the motifs as mimic peptides of native ligands for the epidermal growth factor receptor. Our results indicate that ligand-directed profiling of tumor cell lines can select functional peptides from combinatorial libraries based on the expression of tumor cell surface molecules, which in turn could be exploited as "druggable" receptors in specific types of cancer.

Original languageEnglish (US)
Pages (from-to)34-40
Number of pages7
JournalCancer Research
Volume66
Issue number1
DOIs
StatePublished - Jan 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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