Cytokines in osteoblast-conditioned medium promote the migration of breast cancer cells
TUMOR BIOLOGY
Authors: Chen, Xiaojia; Lu, Jia; Ji, Yuhua; Hong, An; Xie, Qiuling
Abstract
Bone is one of the most common metastatic sites for breast cancer. In this study, we observed a promoting effect of osteoblast-conditioned medium (OCM) on the migration of MCF-7, a noninvasive cell line of breast cancer cells. Cytokine antibody array was used to compare the cytokines of OCM with the conditioned medium of non-differentiated osteoblast cells, which consequently revealed factors related to migration, such as IL8, IL6, CSF2 (G-CSF), CSF3 (GM-CSF), and TNFRSF11B (osteoprotegerin). The expression of genes related to migration was also estimated with a PCR array, which showed that 9 genes were upregulated and 26 genes downregulated. Moreover, activated p38, ERK, and AKT pathways were found in the OCM treatment group. This finding indicated the migration ability of breast cancer cells, which move toward the bone depending on the presence of specific cytokines in its surrounding microenvironment.
Local Production of Osteoprotegerin by Osteoblasts Suppresses Bone Resorption
CELL REPORTS
Authors: Cawley, Keisha M.; Bustamante-Gomez, Nancy Cecile; Guha, Anveshi G.; MacLeod, Ryan S.; Xiong, Jinhu; Gubrij, Igor; Liu, Yu; Mulkey, Robin; Palmieri, Michela; Thostenson, Jeff D.; Goellner, Joseph J.; O'Brien, Charles A.
Abstract
Osteoprotegerin (OPG) inhibits the ability of receptor activator of nuclear factor kappa B (NF-kappa B) ligand (RANKL) to stimulate the differentiation, activity, and survival of bone-resorbing osteoclasts. Genetic studies in mice show that osteocytes are an important source of RANKL, but the cellular sources of OPG are unclear. We use conditional deletion of Tnfrsf11b, which encodes OPG, from different cell populations to identify functionally relevant sources of OPG in mice. Deletion from B lymphocytes and osteocytes, two cell types commonly thought to supply OPG, has little or no impact on bone mass. By contrast, deletion of Tnfrsf11b from osteoblasts increases bone resorption and reduces bone mass to an extent similar to germline deletion, demonstrating that osteoblasts are an essential source of OPG. These results suggest that, in addition to producing new bone matrix, osteoblasts also play an active role in terminating the resorption phase of the bone remodeling cycle by suppressing RANKL activity.
COA
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