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

BMP-7 inhibits TGF-β-induced invasion of breast cancer cells through inhibition of integrin β3 expression - Download this document for free, or read online. Document in PDF available to download.

Cellular Oncology

, Volume 35, Issue 1, pp 19–28

First Online: 21 September 2011Accepted: 23 August 2011DOI: 10.1007-s13402-011-0058-0

Cite this article as: Naber, H.P.H., Wiercinska, E., Pardali, E. et al. Cell Oncol. 2012 35: 19. doi:10.1007-s13402-011-0058-0


BackgroundThe 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.

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

ResultsBMP-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.

ConclusionThus, BMP-7 may exert anti-invasive actions by inhibiting TGF-β-induced expression of integrin β3.

KeywordsBreast cancer Invasion TGF-β BMP-7 Integrin β3 AbbreviationsALKActivin receptor-like kinase

BMPBone Morphogenetic Protein

EMTEpithelial to mesenchymal transition



MMPMatrix metalloproteinase

SmadSma and Mad related gene product

TGF-βTransforming growth factor-β

Hildegonda P. H. Naber and Eliza Wiercinska contributed equally.

Electronic supplementary materialThe online version of this article doi:10.1007-s13402-011-0058-0 contains supplementary material, which is available to authorized users.

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Author: Hildegonda P. H. Naber - Eliza Wiercinska - Evangelia Pardali - Theo van Laar - Ella Nirmala - Anders Sundqvist - Hans v


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