In vivo detection of human TRPV6-rich tumors with anti-cancer peptides derived from soricidin

PLoS One. 2013;8(3):e58866. doi: 10.1371/journal.pone.0058866. Epub 2013 Mar 15.

Abstract

Soricidin is a 54-amino acid peptide found in the paralytic venom of the northern short-tailed shrew (Blarina brevicauda) and has been found to inhibit the transient receptor potential of vallinoid type 6 (TRPV6) calcium channels. We report that two shorter peptides, SOR-C13 and SOR-C27, derived from the C-terminus of soricidin, are high-affinity antagonists of human TRPV6 channels that are up-regulated in a number of cancers. Herein, we report molecular imaging methods that demonstrate the in vivo diagnostic potential of SOR-C13 and SOR-C27 to target tumor sites in mice bearing ovarian or prostate tumors. Our results suggest that these novel peptides may provide an avenue to deliver diagnostic and therapeutic reagents directly to TRPV6-rich tumors and, as such, have potential applications for a range of carcinomas including ovarian, breast, thyroid, prostate and colon, as well as certain leukemia's and lymphomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Female
  • Fluorescent Dyes
  • Gene Expression
  • HEK293 Cells
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Molecular Conformation
  • Molecular Imaging
  • Neoplasms / diagnosis
  • Neoplasms / metabolism
  • Nuclear Magnetic Resonance, Biomolecular
  • Optical Imaging
  • Peptides / chemistry
  • Peptides / metabolism*
  • TRPV Cation Channels / antagonists & inhibitors
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism*
  • Transplantation, Heterologous

Substances

  • Fluorescent Dyes
  • Peptides
  • TRPV Cation Channels
  • TRPV6 channel

Grants and funding

This work was supported by the National Research Council Industrial Research Assistance Program (IRAP) program (http://www.nrc-cnrc.gc.ca/eng/irap/index.html) and Atlantic Canada Opportunities Agency (ACOA) (http://www.acoa-apeca.gc.ca/eng/Pages/Home.aspx) of the Government of Canada. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.