A new non-muscle-invasive bladder tumor-homing peptide identified by phage display in vivo

Oncol Rep. 2016 Jul;36(1):79-89. doi: 10.3892/or.2016.4829. Epub 2016 May 23.

Abstract

Bladder cancer is common and widespread, and its incidence is increasing. Many new diagnostic methods combined with state-of-the-art technology have been introduced in cystoscopy to collect real-time images of the bladder mucosa for diagnosis, but often miss inconspicuous early-stage tumors. Fluorophore-labeled peptides with high sensitivity and specificity for cancer would be a desirable tool for the detection and treatment of tiny or residual bladder tumors. Phage display and the human non-muscle-invasive bladder cancer cell line BIU-87 were used to identify a peptide. The isolated phage display peptide (CSSPIGRHC, named NYZL1) was tested in vitro for its binding specificity and affinity. Accumulation into xenograft tumors in a nude mouse model was analyzed with FITC-labeled NYZL1. NYZL1, with strong tumor‑homing ability, was identified by in vivo phage library selection in the bladder cancer model. The NYZL1 phage and synthetic FITC-labeled NYZL1 peptides bound to tumor tissues and cells, but were hardly detected in normal control organs. Notably, accumulation of FITC-NYZL1 in bladder tumor cells was time-dependent. Biodistribution studies of xenografts of BIU-87 cells showed accumulation of injected FITC-NYZL1 in the tumors, and the bound peptide could not be removed by perfusion after 24 h. The mouse model of bladder tumor showed increased fluorescence intensity in the tumor-bearing bladder in comparison with normal bladder tissues after 4-6 h. In conclusion, NYZL1 may represent a lead peptide structure applicable in the development of optical molecular imaging.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Surface Display Techniques / methods*
  • Fluorescein-5-isothiocyanate / metabolism
  • Fluorescent Dyes / metabolism
  • Heterografts
  • Humans
  • MCF-7 Cells
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Proteins / analysis*
  • Neoplasm Proteins / isolation & purification
  • Neoplasm Transplantation
  • Oligopeptides / analysis*
  • Oligopeptides / isolation & purification
  • Peptide Library
  • Urinary Bladder / pathology
  • Urinary Bladder Neoplasms / diagnosis*
  • Urinary Bladder Neoplasms / pathology*

Substances

  • Fluorescent Dyes
  • Neoplasm Proteins
  • Oligopeptides
  • Peptide Library
  • Fluorescein-5-isothiocyanate