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

Canesin, Giacomo LU ; Evans-Axelsson, Susan LU ; Hellsten, Rebecka LU ; Krzyzanowska, Agnieszka LU ; Prasad, Chandra P. LU ; Bjartell, Anders LU and Andersson, Tommy LU (2017) In PLoS ONE 12(9).
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
WNT5A, Foxy-5, PROSTATE CANCER, Mouse model
in
PLoS ONE
volume
12
issue
9
publisher
Public Library of Science
external identifiers
  • scopus:85029349718
  • pmid:28886116
ISSN
1932-6203
DOI
10.1371/journal.pone.0184418
language
English
LU publication?
yes
id
9947d27b-f78c-49ea-a1de-a6305778a5bb
date added to LUP
2017-10-09 12:00:20
date last changed
2018-05-20 04:37:56
@article{9947d27b-f78c-49ea-a1de-a6305778a5bb,
  abstract     = {<p>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.</p>},
  articleno    = {e0184418},
  author       = {Canesin, Giacomo and Evans-Axelsson, Susan and Hellsten, Rebecka and Krzyzanowska, Agnieszka and Prasad, Chandra P. and Bjartell, Anders and Andersson, Tommy},
  issn         = {1932-6203},
  keyword      = {WNT5A,Foxy-5,PROSTATE CANCER,Mouse model},
  language     = {eng},
  month        = {09},
  number       = {9},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Treatment with the WNT5A-mimicking peptide Foxy-5 effectively reduces the metastatic spread of WNT5A-low prostate cancer cells in an orthotopic mouse model},
  url          = {http://dx.doi.org/10.1371/journal.pone.0184418},
  volume       = {12},
  year         = {2017},
}