Identification of peptides that bind to irradiated pancreatic tumor cells.
OBJECTIVE
Peptides targeting tumor vascular cells or tumor cells themselves have the potential to be used as vectors for delivering either DNA in gene therapy or antitumor agents in chemotherapy. We wished to determine if peptides identified by phage display could be used to target irradiated pancreatic cancer cells.


METHODS
Irradiated Capan-2 cells were incubated with 5 x 10(12) plaque-forming units of a phage display library. Internalized phage were recovered and absorbed against unirradiated cells. After five such cycles of enrichment, the recovered phage were subjected to DNA sequencing analysis and synthetic peptides made. The binding of both phage and synthetic peptides was evaluated by fluorescence staining and flow cytometry in vitro and in vivo.


RESULTS
We identified one 12-mer peptide (PA1) that binds to irradiated Capan-2 pancreatic adenocarcinoma cells but not to unirradiated cells. The binding of peptide was significant after 48 h incubation with cells. In vivo experiments with Capan-2 xenografts in nude mice demonstrated that these small peptides are able to penetrate tumor tissue after intravenous injections and bind specifically to irradiated tumor cells.


CONCLUSIONS
These data suggest that peptides can be identified that target tumors with radiation-induced cell markers and may be clinically useful.
Huang
Canhui
C
Department of Radiation Oncology, The University of Michigan Medical School, Ann Arbor, MI 48109-0010, USA.
Liu
Xiang Y
XY
Rehemtulla
Alnawaz
A
Lawrence
Theodore S
TS
D000818:Animals; D001435:Bacteriophages / Q000235:genetics / Q000254:growth & development; D045744:Cell Line, Tumor / Q000378:metabolism / Q000528:radiation effects; D003080:Cold Temperature; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D019151:Peptide Library; D010455:Peptides / Q000302:isolation & purification / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D010948:Viral Plaque Assay / Q000379:methods
D019151:Peptide Library; D010455:Peptides; D016650:Fluorescein-5-isothiocyanate