This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Säfholm, A. Articles by Andersson, T. Search for Related Content PubMed PubMed Citation Articles by Säfholm, A. Articles by Andersson, T.

The Wnt-5a–Derived Hexapeptide Foxy-5 Inhibits Breast Cancer Metastasis In vivo by Targeting Cell Motility

Authors' Affiliations: ¹ Cell and Experimental Pathology and ² Tumor Biology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden; and ³ Department of Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland

Requests for reprints: Tommy Andersson, Department of Laboratory Medicine, Lund University, UMAS, CRC, Entrance 72, Building 91, Fl 11, SE-205 02 Malmö, Sweden. Phone: 46-40391167; Fax: 46-40391177; E-mail: tommy.andersson{at}med.lu.se.

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.

This article has been cited by other articles:

				C. E. Ford, E. J. Ekstrom, and T. Andersson From the Cover: Wnt-5a signaling restores tamoxifen sensitivity in estrogen receptor-negative breast cancer cells PNAS, March 10, 2009; 106(10): 3919 - 3924. [Abstract] [Full Text] [PDF]