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BMP-7 inhibits TGF-β-induced invasion of breast cancer cells through inhibition of integrin β(3) expression
Department of Molecular Cell Biology and Centre for Biomedical Genetics, Leiden University Medical Center, Postzone S-1-P, PO Box 9600, 2300 RC Leiden, The Netherlands.
Department of Molecular Cell Biology and Centre for Biomedical Genetics, Leiden University Medical Center, Postzone S-1-P, PO Box 9600, 2300 RC Leiden, The Netherlands.
Department of Molecular Cell Biology and Centre for Biomedical Genetics, Leiden University Medical Center, Postzone S-1-P, PO Box 9600, 2300 RC Leiden, The Netherlands.
Department of Molecular Cell Biology and Centre for Biomedical Genetics, Leiden University Medical Center, Postzone S-1-P, PO Box 9600, 2300 RC Leiden, The Netherlands.
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2012 (English)In: Cellular Oncology, ISSN 2211-3428, E-ISSN 2211-3436, Vol. 35, no 1, 19-28 p.Article in journal (Refereed) Published
Abstract [en]

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 α(v)β(3) in the spheroids. Moreover, targeting of integrins by a chemical inhibitor or knockdown of integrin β(3) negatively affected TGF-β-induced invasion. On the other hand, overexpression of integrin β(3) 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 β(3).

Place, publisher, year, edition, pages
Springer , 2012. Vol. 35, no 1, 19-28 p.
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Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-168807DOI: 10.1007/s13402-011-0058-0ISI: 000299920300003PubMedID: 21935711OAI: oai:DiVA.org:uu-168807DiVA: diva2:503458
Available from: 2012-02-15 Created: 2012-02-15 Last updated: 2017-12-07Bibliographically approved

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Sundqvist, Andersten Dijke, Peter

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