Ligand-directed surface profiling of human cancer cells with combinatorial peptide libraries.
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.
Kolonin
Mikhail G
MG
The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Bover
Laura
L
Sun
Jessica
J
Zurita
Amado J
AJ
Do
Kim-Anh
KA
Lahdenranta
Johanna
J
Cardó-Vila
Marina
M
Giordano
Ricardo J
RJ
Jaalouk
Diana E
DE
Ozawa
Michael G
MG
Moya
Catherine A
CA
Souza
Glauco R
GR
Staquicini
Fernanda I
FI
Kunyiasu
Akihiko
A
Scudiero
Dominic A
DA
Holbeck
Susan L
SL
Sausville
Edward A
EA
Arap
Wadih
W
Pasqualini
Renata
R
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D016000:Cluster Analysis; D020650:Combinatorial Chemistry Techniques; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism; D019151:Peptide Library; D010455:Peptides / Q000378:metabolism*; D015203:Reproducibility of Results
D008024:Ligands; D009363:Neoplasm Proteins; D009842:Oligopeptides; D019151:Peptide Library; D010455:Peptides; C047981:arginyl-glycyl-aspartic acid; D066246:ErbB Receptors