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BMP-7 inhibits TGF-β-induced invasion of breast cancer cells through inhibition of integrin β(3) expression

Naber, Hildegonda P H (författare)
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
Wiercinska, Eliza (författare)
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
Pardali, Evangelia (författare)
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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van Laar, Theo (författare)
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
Nirmala, Ella (författare)
Division of Toxicology, Leiden Amsterdam Center for Drug Research, Leiden University, Einsteinweg 55, 2300 RA Leiden, The Netherlands
Sundqvist, Anders (författare)
Uppsala universitet,Ludwiginstitutet för cancerforskning
van Dam, Hans (författare)
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
van der Horst, Geertje (författare)
Department of Urology and Endocrinology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
van der Pluijm, Gabri (författare)
Department of Urology and Endocrinology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
Heckmann, Bertrand (författare)
Galapagos SASU, 102 Avenue Gaston Roussel, 93230 Romainville, France
Danen, Erik H J (författare)
Division of Toxicology, Leiden Amsterdam Center for Drug Research, Leiden University, Einsteinweg 55, 2300 RA Leiden, The Netherlands
ten Dijke, Peter (författare)
Uppsala universitet,Ludwiginstitutet för cancerforskning
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 (creator_code:org_t)
2011-09-21
2012
Engelska.
Ingår i: Cellular Oncology. - : Springer. - 2211-3428 .- 2211-3436. ; 35:1, s. 19-28
Relaterad länk:
https://link.springe...
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https://urn.kb.se/re...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • 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).

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