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Cellular Oncology
Published in: Cellular Oncology 1/2012

Open Access 01-02-2012 | Original Paper

BMP-7 inhibits TGF-β-induced invasion of breast cancer cells through inhibition of integrin β3 expression

Authors: Hildegonda P. H. Naber, Eliza Wiercinska, Evangelia Pardali, Theo van Laar, Ella Nirmala, Anders Sundqvist, Hans van Dam, Geertje van der Horst, Gabri van der Pluijm, Bertrand Heckmann, Erik H. J. Danen, Peter ten Dijke

Published in: Cellular Oncology | Issue 1/2012

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Abstract

Background

The transforming growth factor (TGF)-β superfamily comprises cytokines such as TGF-β and Bone Morphogenetic Proteins (BMPs), which have a critical role in a multitude of biological processes. In breast cancer, high levels of TGF-β are associated with poor outcome, whereas inhibition of TGF-β-signaling reduces metastasis. In contrast, BMP-7 inhibits bone metastasis of breast cancer cells.

Methods

In this study, we investigated the effect of BMP-7 on TGF-β-induced invasion in a 3 dimensional invasion assay.

Results

BMP-7 inhibited TGF-β-induced invasion of the metastatic breast cancer cell line MCF10CA1a, but not of its premalignant precursor MCF10AT in a spheroid invasion model. The inhibitory effect appears to be specific for BMP-7, as its closest homolog, BMP-6, did not alter the invasion of MCF10CA1a spheroids. To elucidate the mechanism by which BMP-7 inhibits TGF-β-induced invasion, we analyzed invasion-related genes. BMP-7 inhibited TGF-β-induced expression of integrin αvβ3 in the spheroids. Moreover, targeting of integrins by a chemical inhibitor or knockdown of integrin β3 negatively affected TGF-β-induced invasion. On the other hand, overexpression of integrin β3 counteracted the inhibitory effect of BMP7 on TGF-β-induced invasion.

Conclusion

Thus, BMP-7 may exert anti-invasive actions by inhibiting TGF-β-induced expression of integrin β3.
Appendix
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Metadata
Title
BMP-7 inhibits TGF-β-induced invasion of breast cancer cells through inhibition of integrin β3 expression
Authors
Hildegonda P. H. Naber
Eliza Wiercinska
Evangelia Pardali
Theo van Laar
Ella Nirmala
Anders Sundqvist
Hans van Dam
Geertje van der Horst
Gabri van der Pluijm
Bertrand Heckmann
Erik H. J. Danen
Peter ten Dijke
Publication date
01-02-2012
Publisher
Springer Netherlands
Published in
Cellular Oncology / Issue 1/2012
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-011-0058-0

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