Treatment with the WNT5A-mimicking peptide Foxy-5 effectively reduces the metastatic spread of WNT5A-low prostate cancer cells in an orthotopic mouse model

PLoS One. 2017 Sep 8;12(9):e0184418. doi: 10.1371/journal.pone.0184418. eCollection 2017.


Prostate cancer patients with high WNT5A expression in their tumors have been shown to have more favorable prognosis than those with low WNT5A expression. This suggests that reconstitution of Wnt5a in low WNT5A-expressing tumors might be an attractive therapeutic approach. To explore this idea, we have in the present study used Foxy-5, a WNT5A mimicking peptide, to investigate its impact on primary tumor and metastasis in vivo and on prostate cancer cell viability, apoptosis and invasion in vitro. We used an in vivo orthotopic xenograft mouse model with metastatic luciferase-labeled WNT5A-low DU145 cells and metastatic luciferase-labeled WNT5A-high PC3prostate cancer cells. We provide here the first evidence that Foxy-5 significantly inhibits the initial metastatic dissemination of tumor cells to regional and distal lymph nodes by 90% and 75%, respectively. Importantly, this effect was seen only with the WNT5A-low DU145 cells and not with the WNT5A-high PC3 cells. The inhibiting effect in the DU145-based model occurred despite the fact that no effects were observed on primary tumor growth, apoptosis or proliferation. These findings are consistent with and supported by the in vitro data, where Foxy-5 specifically targets invasion without affecting apoptosis or viability of WNT5A-low prostate cancer cells. To conclude, our data indicate that the WNT5A-mimicking peptide Foxy-5, which has been recently used in a phase 1 clinical trial, is an attractive candidate for complimentary anti-metastatic treatment of prostate cancer patients with tumors exhibiting absent or low WNT5A expression.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Humans
  • Male
  • Mice
  • Molecular Mimicry*
  • Neoplasm Metastasis
  • Oligopeptides / pharmacology*
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology*
  • Wnt-5a Protein / chemistry*
  • Wnt-5a Protein / metabolism*
  • Xenograft Model Antitumor Assays


  • Foxy-5 peptide
  • Oligopeptides
  • WNT5A protein, human
  • Wnt-5a Protein

Grants and funding

This work was supported by the Swedish Cancer Foundation ( to TA (140643) and to AB (140274), the Swedish Research Council ( to TA (B0434701) and to AB (D0484201), the BioCare program at Lund University ( to TA, the Skåne University Hospital Research Foundation, the Gunnar Nilsson’s Cancer Foundation ( and Governmental Funding of Clinical Research within the National Health Services (ALF) all to TA and AB, and the Royal Physiographic Society ( to GC. The funding sources had no role in the study design, data collection and analysis, the decision to publish, or in the preparation of the manuscript.