Screening of an annexin-A2-targeted heptapeptide for pancreatic adenocarcinoma localization

Mol Oncol. 2023 May;17(5):872-886. doi: 10.1002/1878-0261.13352. Epub 2022 Dec 30.

Abstract

Annexin A2 (ANXA2) encodes an oncoprotein whose expression has been found to correlate with poorer overall survival (OS) of pancreatic adenocarcinoma (PAAD) patients. Although peptides are available for targeting ANXA2, none of these were initially selected to target this protein specifically. Here, we took ANXA2 as a molecular target for PAAD and employed the phage display technique to screen for a new ANXA2-targeted peptide. The resultant heptapeptide, YW7, was firstly labeled with fluorescein isothiocyanate (FITC) to evaluate its selectivity in cellular uptake, and further with the near-infrared fluorescent (NIRF) dye Cy7 to assess in vivo distribution in a mouse model bearing PANC-1 human pancreatic cancer xenografic tumors. We found that both FITC-YW7 and Cy7-YW7 probes showed significantly higher uptake in PANC-1 cells compared to the HPDE6-C7 pancreatic epithelium cells. Mice intravenously injected with Cy7-YW7 showed higher tumor-to-background ratios (TBRs) (~ 2.7-fold) in tumor tissues compared to those injected with Cy7 alone. Our study suggested that YW7 is a novel peptide targeting ANXA2 and Cy7-YW7 is an NIRF probe potentially useful for the early detection of PAAD.

Keywords: ANXA2; imaging; near-infrared fluorescent; pancreatic adenocarcinoma; peptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma*
  • Animals
  • Annexin A2* / metabolism
  • Cell Line, Tumor
  • Fluorescein-5-isothiocyanate
  • Humans
  • Mice
  • Pancreatic Neoplasms* / pathology
  • Peptides

Substances

  • Annexin A2
  • Fluorescein-5-isothiocyanate
  • Peptides