期刊
CELLULAR ONCOLOGY
卷 35, 期 1, 页码 19-28出版社
SPRINGER
DOI: 10.1007/s13402-011-0058-0
关键词
Breast cancer; Invasion; TGF-beta; BMP-7; Integrin beta(3)
资金
- Tumor Host Genomics [518198]
- Centre for Biomedical Genetics
- Swedish Cancerfonden [09 0773]
The transforming growth factor (TGF)-beta superfamily comprises cytokines such as TGF-beta and Bone Morphogenetic Proteins (BMPs), which have a critical role in a multitude of biological processes. In breast cancer, high levels of TGF-beta are associated with poor outcome, whereas inhibition of TGF-beta-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-beta-induced invasion in a 3 dimensional invasion assay. BMP-7 inhibited TGF-beta-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-beta-induced invasion, we analyzed invasion-related genes. BMP-7 inhibited TGF-beta-induced expression of integrin alpha(v)beta(3) in the spheroids. Moreover, targeting of integrins by a chemical inhibitor or knockdown of integrin beta(3) negatively affected TGF-beta-induced invasion. On the other hand, overexpression of integrin beta(3) counteracted the inhibitory effect of BMP7 on TGF-beta-induced invasion. Thus, BMP-7 may exert anti-invasive actions by inhibiting TGF-beta-induced expression of integrin beta(3).
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