title: Biological roles of human bone morphogenetic protein 9 in the bone microenvironment of human breast cancer MDA-MB-231 cells.
abstract: Bone marrow stroma plays a critical role in the bone metastasis of breast cancer. Bone marrow-derived mesenchymal stem cells (BMSC) are critical to facilitate cancer progression. Human bone morphogenetic protein 9 (BMP9) is the most potent osteogenic factor and one of bone-stored growth factors involved in both promotion and inhibition of different cancers. However, it is unclear whether BMP9 correlates with the bone metastasis of breast cancer. This study was to evaluate the role of BMP9 in the interaction between BMSC and breast cancer cells (BCC). To determine whether BMP9 is able to block the tumor promoting effect of BMSC, an in vitro model was developed using breast cancer MDA-MB-231 cells co-cultured with bone marrow-derived mesenchymal stem cells HS-5 with-BMP9 overexpression. The expressions of metastasis-related genes were detected to identify important factors mediating the role of BMP9 in breast cancer cells. Results showed BMP9 could inhibit invasion and promote apoptosis of MDA-MB-231 cells. The expressions of interleukin-6 (IL-6), matrix metalloproteinase-2 (MMP-2) and monocyte chemoattratctant protein-1 (MCP-1) decreased in the MDA-MB-231 cells of BMP9 over-expression group, and the expressions of epithelial-mesenchymal transition (EMT)-related molecules was also reduced. On the other hand, the expression of stromal cell derived factor-1 (SDF-1) decreased in HS-5 cells of BMP9 over-expression group. Taken together, BMP9 is able to inhibit the migration and promote the apoptosis of breast cancer by regulating the interaction between MDA-MB-231 cells and HS-5 cells in which SDF-1/CXCR4-PI3K pathway and EMT are involved.
authors.affiliation: Key Laboratory of Diagnostic Medicine of The Chinese Ministry of Education, School of Clinical Diagnostic and Laboratory Medicine, Chongqing Medical University No.1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Key Laboratory of Diagnostic Medicine of The Chinese Ministry of Education, School of Clinical Diagnostic and Laboratory Medicine, Chongqing Medical University No.1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China.
authors.forename: Yaguang
authors.initials: Y
authors.lastname: Weng
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Chongqing Medical University No.1 Youyi Road, Yuzhong District, Chongqing 400042, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ren
authors.affiliation: Key Laboratory of Diagnostic Medicine of The Chinese Ministry of Education, School of Clinical Diagnostic and Laboratory Medicine, Chongqing Medical University No.1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Diagnostic Medicine of The Chinese Ministry of Education, School of Clinical Diagnostic and Laboratory Medicine, Chongqing Medical University No.1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Key Laboratory of Diagnostic Medicine of The Chinese Ministry of Education, School of Clinical Diagnostic and Laboratory Medicine, Chongqing Medical University No.1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China.
authors.forename: Jinshu
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Diagnostic Medicine of The Chinese Ministry of Education, School of Clinical Diagnostic and Laboratory Medicine, Chongqing Medical University No.1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China.
authors.forename: Yayun
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Diagnostic Medicine of The Chinese Ministry of Education, School of Clinical Diagnostic and Laboratory Medicine, Chongqing Medical University No.1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Diagnostic Medicine of The Chinese Ministry of Education, School of Clinical Diagnostic and Laboratory Medicine, Chongqing Medical University No.1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Molecular Oncology Laboratory, Department of Surgery, University of Chicago Medical Center Chicago, IL, USA.
authors.forename: Tongchuan
authors.initials: T
authors.lastname: He
authors.affiliation: Key Laboratory of Diagnostic Medicine of The Chinese Ministry of Education, School of Clinical Diagnostic and Laboratory Medicine, Chongqing Medical University No.1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
keywords: Bone morphogenetic protein 9; SDF-1/CXCR4-PI3K pathway; bone metastasis; breast cancer; epithelial-mesenchymal transition