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The Wnt-5a-derived hexapeptide Foxy-5 inhibits breast cancer metastasis in vivo by targeting cell motility.

Säfholm, Annette LU ; Tuomela, Johanna; Rosenkvist, Jeanette LU ; Sand-Dejmek, Janna LU ; Härkönen, Pirkko LU and Andersson, Tommy LU (2008) In Clinical Cancer Research 14(20). p.6556-6563
Abstract
PURPOSE: An inherent problem in breast cancer treatment is that current therapeutic approaches fail to specifically target the dissemination of breast cancer cells from the primary tumor. Clinical findings show that the loss of Wnt-5a protein expression in the primary breast tumor predicts a faster tumor spread, and in vitro analyses reveal that it does so by inhibiting tumor cell migration. Therefore, we hypothesized that the reconstitution of Wnt-5a signaling could be a novel therapeutic strategy to inhibit breast cancer metastasis. EXPERIMENTAL DESIGN: We used in vitro techniques to show that 4T1 mouse breast cancer cells responded to the reconstitution of Wnt-5a signaling using our novel Wnt-5a mimicking hexapeptide, Foxy-5, in the... (More)
PURPOSE: An inherent problem in breast cancer treatment is that current therapeutic approaches fail to specifically target the dissemination of breast cancer cells from the primary tumor. Clinical findings show that the loss of Wnt-5a protein expression in the primary breast tumor predicts a faster tumor spread, and in vitro analyses reveal that it does so by inhibiting tumor cell migration. Therefore, we hypothesized that the reconstitution of Wnt-5a signaling could be a novel therapeutic strategy to inhibit breast cancer metastasis. EXPERIMENTAL DESIGN: We used in vitro techniques to show that 4T1 mouse breast cancer cells responded to the reconstitution of Wnt-5a signaling using our novel Wnt-5a mimicking hexapeptide, Foxy-5, in the same way as human breast cancer cells. Therefore, we could subsequently study its effect in vivo on the metastatic spread of cancer following the inoculation of 4T1 cells into mice. RESULTS: In vitro analyses revealed that both recombinant Wnt-5a and the Wnt-5a-derived Foxy-5 peptide impaired migration and invasion without affecting apoptosis or proliferation of 4T1 breast cancer cells. The in vivo experiments show that i.p. injections of Foxy-5 inhibited metastasis of inoculated 4T1 breast cancer cells from the mammary fat pad to the lungs and liver by 70% to 90%. CONCLUSIONS: These data provide proof of principle that the reconstitution of Wnt-5a signaling in breast cancer cells is a novel approach to impair breast tumor metastasis by targeting cell motility. In combination with existing therapies, this approach represents a potential novel therapeutic strategy for the treatment of breast cancer patients. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical Cancer Research
volume
14
issue
20
pages
6556 - 6563
publisher
American Association for Cancer Research
external identifiers
  • wos:000260359600025
  • pmid:18927296
  • scopus:58149190789
ISSN
1078-0432
DOI
10.1158/1078-0432.CCR-08-0711
language
English
LU publication?
yes
id
8829de30-7ec6-416b-9873-d5e7fc79afbf (old id 1262148)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18927296?dopt=Abstract
date added to LUP
2008-11-03 13:03:59
date last changed
2017-11-12 04:07:13
@article{8829de30-7ec6-416b-9873-d5e7fc79afbf,
  abstract     = {PURPOSE: An inherent problem in breast cancer treatment is that current therapeutic approaches fail to specifically target the dissemination of breast cancer cells from the primary tumor. Clinical findings show that the loss of Wnt-5a protein expression in the primary breast tumor predicts a faster tumor spread, and in vitro analyses reveal that it does so by inhibiting tumor cell migration. Therefore, we hypothesized that the reconstitution of Wnt-5a signaling could be a novel therapeutic strategy to inhibit breast cancer metastasis. EXPERIMENTAL DESIGN: We used in vitro techniques to show that 4T1 mouse breast cancer cells responded to the reconstitution of Wnt-5a signaling using our novel Wnt-5a mimicking hexapeptide, Foxy-5, in the same way as human breast cancer cells. Therefore, we could subsequently study its effect in vivo on the metastatic spread of cancer following the inoculation of 4T1 cells into mice. RESULTS: In vitro analyses revealed that both recombinant Wnt-5a and the Wnt-5a-derived Foxy-5 peptide impaired migration and invasion without affecting apoptosis or proliferation of 4T1 breast cancer cells. The in vivo experiments show that i.p. injections of Foxy-5 inhibited metastasis of inoculated 4T1 breast cancer cells from the mammary fat pad to the lungs and liver by 70% to 90%. CONCLUSIONS: These data provide proof of principle that the reconstitution of Wnt-5a signaling in breast cancer cells is a novel approach to impair breast tumor metastasis by targeting cell motility. In combination with existing therapies, this approach represents a potential novel therapeutic strategy for the treatment of breast cancer patients.},
  author       = {Säfholm, Annette and Tuomela, Johanna and Rosenkvist, Jeanette and Sand-Dejmek, Janna and Härkönen, Pirkko and Andersson, Tommy},
  issn         = {1078-0432},
  language     = {eng},
  number       = {20},
  pages        = {6556--6563},
  publisher    = {American Association for Cancer Research},
  series       = {Clinical Cancer Research},
  title        = {The Wnt-5a-derived hexapeptide Foxy-5 inhibits breast cancer metastasis in vivo by targeting cell motility.},
  url          = {http://dx.doi.org/10.1158/1078-0432.CCR-08-0711},
  volume       = {14},
  year         = {2008},
}