Targeting bladder tumor cells in vivo and in the urine with a peptide identified by phage display

Seung Min Lee, Eun Ju Lee, Hai Yan Hong, Mi Kyung Kwon, Tae Hwan Kwon, Je Yong Choi, Rang Woon Park, Tae Gyun Kwon, Eun Sang Yoo, Gil Suk Yoon, In San Kim, Erkki Ruoslahti, Byung Heon Lee

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Bladder cancer is one of the most common tumors of the genitourinary tract. Here, we use phage display to identify a peptide that targets bladder tumor cells. A phage library containing random peptides was screened for binding to cells from human bladder tumor xenografts. Phage clones were further selected for binding to a bladder tumor cell line in culture. Six clones displaying the consensus sequence CXNXDXRX/RC showed selective binding to cells from primary human bladder cancer tissue. Of these, the CSNRDARRC sequence was selected for further study as a synthetic peptide. Fluorescein-conjugated CSNRDARRC peptide selectively bound to frozen sections of human bladder tumor tissue, whereas only negligible binding to normal bladder tissue was observed. When the fluorescent peptide was introduced into the bladder lumen, in a carcinogen-induced rat tumor model, it selectively bound to tumor epithelium. Moreover, when the peptide was intravenously injected into the tail vein, it homed to the bladder tumor but was not detectable in normal bladder and control organs. Next, we examined whether the peptide can detect tumor cells in urine. The fluorescent peptide bound to cultured bladder tumor cells but not to other types of tumor cell lines. Moreover, it bound to urinary cells of patients with bladder cancer, while showing little binding to urinary cells of patients with inflammation or healthy individuals. The CSNRDARRC peptide may be useful as a targeting moiety for selective delivery of therapeutics and as a diagnostic probe for the detection of bladder cancer.

Original languageEnglish
Pages (from-to)11-19
Number of pages9
JournalMolecular Cancer Research
Volume5
Issue number1
DOIs
Publication statusPublished - 2007 Jan
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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  • Cite this

    Lee, S. M., Lee, E. J., Hong, H. Y., Kwon, M. K., Kwon, T. H., Choi, J. Y., Park, R. W., Kwon, T. G., Yoo, E. S., Yoon, G. S., Kim, I. S., Ruoslahti, E., & Lee, B. H. (2007). Targeting bladder tumor cells in vivo and in the urine with a peptide identified by phage display. Molecular Cancer Research, 5(1), 11-19. https://doi.org/10.1158/1541-7786.MCR-06-0069