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[Cancer Research 66, 34-40, January 1, 2006]
© 2006 American Association for Cancer Research


Priority Reports

Ligand-Directed Surface Profiling of Human Cancer Cells with Combinatorial Peptide Libraries

Mikhail G. Kolonin1, Laura Bover1, Jessica Sun1, Amado J. Zurita1, Kim-Anh Do1, Johanna Lahdenranta1, Marina Cardó-Vila1, Ricardo J. Giordano1, Diana E. Jaalouk1, Michael G. Ozawa1, Catherine A. Moya1, Glauco R. Souza1, Fernanda I. Staquicini1, Akihiko Kunyiasu1, Dominic A. Scudiero2, Susan L. Holbeck2, Edward A. Sausville2, Wadih Arap1 and Renata Pasqualini1

1 The University of Texas M.D. Anderson Cancer Center, Houston, Texas; and 2 Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, Bethesda, Maryland

Requests for reprints: Renata Pasqualini or Wadih Arap, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: 713-792-3873; Fax: 713-745-2999; E-mail: rpasqual{at}mdanderson.org; warap{at}mdanderson.org.

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. (Cancer Res 2006; 66(1): 34-40)




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
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Copyright © 2006 by the American Association for Cancer Research.