
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.In this study, we investigated the effect of BMP-7 on TGF-β-induced invasion in a 3 dimensional invasion assay.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.Thus, BMP-7 may exert anti-invasive actions by inhibiting TGF-β-induced expression of integrin β(3).
Medicine(all), Original Paper, Bone Morphogenetic Protein 6, Bone Morphogenetic Protein 7, Integrin beta3, Breast Neoplasms, Smad Proteins, Integrin alpha5, Gene Expression Regulation, Neoplastic, Transforming Growth Factor beta, Cell Line, Tumor, Humans, Matrix Metalloproteinase 2, Female, Neoplasm Invasiveness, Neoplasm Metastasis, Carrier Proteins, Cell Proliferation, Signal Transduction
Medicine(all), Original Paper, Bone Morphogenetic Protein 6, Bone Morphogenetic Protein 7, Integrin beta3, Breast Neoplasms, Smad Proteins, Integrin alpha5, Gene Expression Regulation, Neoplastic, Transforming Growth Factor beta, Cell Line, Tumor, Humans, Matrix Metalloproteinase 2, Female, Neoplasm Invasiveness, Neoplasm Metastasis, Carrier Proteins, Cell Proliferation, Signal Transduction
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