title: BMP9 inhibits the bone metastasis of breast cancer cells by downregulating CCN2 (connective tissue growth factor, CTGF) expression.
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.
authors.affiliation: Department of General Surgery, The First Affiliated Hospitals of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ren
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Sun
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.forename: Honglei
authors.initials: H
authors.lastname: Feng
authors.forename: Yuehong
authors.initials: Y
authors.lastname: Liu
authors.forename: Chang
authors.initials: C
authors.lastname: Fei
authors.forename: Shaoheng
authors.initials: S
authors.lastname: Wan
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Jinyong
authors.initials: J
authors.lastname: Luo
authors.forename: Qiong
authors.initials: Q
authors.lastname: Shi
authors.forename: Min
authors.initials: M
authors.lastname: Tang
authors.forename: Guowei
authors.initials: G
authors.lastname: Zuo
authors.forename: Yaguang
authors.initials: Y
authors.lastname: Weng
authors.forename: Tongchuan
authors.initials: T
authors.lastname: He
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D001859:Bone Neoplasms / Q000556:secondary; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans
chemical_list: C526317:CCN2 protein, human; C525887:GDF2 protein, human; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors; D055513:Connective Tissue Growth Factor