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.