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BMP9 inhibits the bone metastasis of breast cancer cells by downregulating CCN2 (connective tissue growth factor, CTGF) expression

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Abstract

Bone morphogenetic proteins (BMPs), which belong to the transforming growth factor-β superfamily, regulate a wide range of cellular responses including cell proliferation, differentiation, adhesion, migration, and apoptosis. BMP9, the latest BMP to be discovered, is reportedly expressed in a variety of human carcinoma cell lines, but the role of BMP9 in breast cancer has not been fully clarified. In a previous study, BMP9 was found to inhibit the growth, migration, and invasiveness of MDA-MB-231 breast cancer cells. In the current study, the effect of BMP9 on the bone metastasis of breast cancer cells was investigated. After absent or low expression of BMP9 was detected in the MDA-MB-231 breast cancer cells and breast non-tumor adjacent tissues using Western blot and immunohistochemistry, In our previous study, BMP9 could inhibit the proliferation and invasiveness of breast cancer cells MDA-MB-231 in vitro and in vivo. This paper shows that BMP9 inhibit the bone metastasis of breast cancer cells by activating the BMP/Smad signaling pathway and downregulating connective tissue growth factor (CTGF); however, when CTGF expression was maintained, the inhibitory effect of BMP9 on the MDA-MB-231 cells was abolished. Together, these observations indicate that BMP9 is an important mediator of breast cancer bone metastasis and a potential therapeutic target for treating this deadly disease.

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Acknowledgments

We thank Dr. Liu Shengchun (the First Affiliated Hospital of Chongqing Medical University) for the human breast cancer tissue samples. The present study was supported by the National Natural Science Foundation of China (Grant No. 81172017), the National Natural Science Foundation of China (Grant No. 30800658) and the Natural Science Foundation Project of Chongqing Science and Technology Commission (Grant No. 2009BB5060).

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Authors and Affiliations

  1. Department of General Surgery, The First Affiliated Hospitals of Chongqing Medical University, Chongqing, 400016, China

    Wei Ren

  2. Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, 1 YiXueYuan Road, Yuzhong District, Chongqing, 400016, China

    Xiaoxiao Sun, Ke Wang, Honglei Feng, Yuehong Liu, Chang Fei, Shaoheng Wan, Wei Wang, Jinyong Luo, Qiong Shi, Min Tang, Guowei Zuo, Yaguang Weng & Yan Zhang

  3. Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL, USA

    Tongchuan He

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  1. Wei Ren
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Correspondence to Yan Zhang.

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Wei Ren and Xiaoxiao Sun have contributed equally to this work.

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Ren, W., Sun, X., Wang, K. et al. BMP9 inhibits the bone metastasis of breast cancer cells by downregulating CCN2 (connective tissue growth factor, CTGF) expression. Mol Biol Rep 41, 1373–1383 (2014). https://doi.org/10.1007/s11033-013-2982-8

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  • DOI: https://doi.org/10.1007/s11033-013-2982-8

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