Identification of a met-binding peptide from a phage display library.
Clin Cancer Res
; 13(20): 6049-55, 2007 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-17947467
ABSTRACT
PURPOSE:
Aberrant c-Met expression has been implicated in most types of human cancer. We are developing Met-directed imaging and therapeutic agents. EXPERIMENTALDESIGN:
To seek peptides that bind specifically to receptor Met, the Met-expressing cell lines S114 and SK-LMS-1 were used for biopanning with a random peptide phage display library. Competition ELISA, fluorescence-activated cell sorting analysis, an internalization assay, and a cell proliferation assay were used to characterize a Met-binding peptide in vitro. To evaluate the utility of the peptide as a diagnostic agent in vivo, 125I-labeled peptide was injected i.v. into nude mice bearing s.c. xenografts of the Met-expressing and hepatocyte growth factor (HGF)/scatter factor-expressing SK-LMS-1/HGF, and total body scintigrams were obtained between 1 and 24 h postinjection.RESULTS:
One Met-binding peptide (YLFSVHWPPLKA), designated Met-pep1, reacts with Met on the cell surface and competes with HGF/scatter factor binding to Met in a dose-dependent manner. Met-pep1 is internalized by Met-expressing cells after receptor binding. Met-pep1 inhibits human leiomyosarcoma SK-LMS-1 cell proliferation in vitro. In SK-LMS-1 mouse xenografts, tumor-associated activity was imaged as early as 1 h postinjection and remained visible in some animals as late as 24 h postinjection.CONCLUSIONS:
Met-pep1 specifically interacts with Met it is internalized by Met-expressing cells and inhibits tumor cell proliferation in vitro; it is a potential diagnostic agent for tumor imaging.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação Neoplásica da Expressão Gênica
/
Biblioteca de Peptídeos
/
Proteínas Proto-Oncogênicas c-met
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Clin Cancer Res
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos