Lani
11-03-2007, 10:48 AM
Exp Cell Res. 2007 Oct 4; [Epub ahead of print]
Metastatic breast cancer induces an osteoblast inflammatory response.
Kinder M, Chislock E, Bussard KM, Shuman L, Mastro AM.
Department of Biochemistry and Molecular Biology, The Pennsylvania State University, 431 S. Frear Building, University Park, PA 16802, USA.
Breast cancer preferentially metastasizes to the skeleton, a hospitable environment that attracts and allows breast cancer cells to thrive. Growth factors released as bone is degraded support tumor cell growth, and establish a cycle favoring continued bone degradation. While the osteoclasts are the direct effectors of bone degradation, we found that osteoblasts also contribute to bone loss. Osteoblasts are more than intermediaries between tumor cells and osteoclasts. We have presented evidence that osteoblasts contribute through loss of function induced by metastatic breast cancer cells. Metastatic breast cancer cells suppress osteoblast differentiation, alter morphology, and increase apoptosis. In this study we show that osteoblasts undergo an inflammatory stress response in the presence of human metastatic breast cancer cells. When conditioned medium from cancer cells was added to human osteoblasts, the osteoblasts were induced to express increased levels of IL-6, IL-8, and MCP-1; cytokines known to attract, differentiate, and activate osteoclasts. Similar findings were seen with murine osteoblasts and primary murine calvarial osteoblasts. Osteoblasts are co-opted into creating a microenvironment that exacerbates bone loss and are prevented from producing matrix proteins for mineralization. This is the first study implicating osteoblast produced IL-6, IL-8 (human; MIP-2 and KC mouse), and MCP-1 as key mediators in the osteoblast response to metastatic breast cancer cells.
PMID: 17976581 [PubMed - as supplied by publisher]
translation--breast cancer cells act not only in ways that increase the activity of bone dissolving cells, they also cause bone forming cells to secrete compounds which attract, increase the numbers and activity of the bone disolving cells as well as keeping them from making the scaffolding onto which bone mineral is laid down. This new understanding may lead to better treatments. Until now they thought only the bone dissolving cells were the culprits.
Metastatic breast cancer induces an osteoblast inflammatory response.
Kinder M, Chislock E, Bussard KM, Shuman L, Mastro AM.
Department of Biochemistry and Molecular Biology, The Pennsylvania State University, 431 S. Frear Building, University Park, PA 16802, USA.
Breast cancer preferentially metastasizes to the skeleton, a hospitable environment that attracts and allows breast cancer cells to thrive. Growth factors released as bone is degraded support tumor cell growth, and establish a cycle favoring continued bone degradation. While the osteoclasts are the direct effectors of bone degradation, we found that osteoblasts also contribute to bone loss. Osteoblasts are more than intermediaries between tumor cells and osteoclasts. We have presented evidence that osteoblasts contribute through loss of function induced by metastatic breast cancer cells. Metastatic breast cancer cells suppress osteoblast differentiation, alter morphology, and increase apoptosis. In this study we show that osteoblasts undergo an inflammatory stress response in the presence of human metastatic breast cancer cells. When conditioned medium from cancer cells was added to human osteoblasts, the osteoblasts were induced to express increased levels of IL-6, IL-8, and MCP-1; cytokines known to attract, differentiate, and activate osteoclasts. Similar findings were seen with murine osteoblasts and primary murine calvarial osteoblasts. Osteoblasts are co-opted into creating a microenvironment that exacerbates bone loss and are prevented from producing matrix proteins for mineralization. This is the first study implicating osteoblast produced IL-6, IL-8 (human; MIP-2 and KC mouse), and MCP-1 as key mediators in the osteoblast response to metastatic breast cancer cells.
PMID: 17976581 [PubMed - as supplied by publisher]
translation--breast cancer cells act not only in ways that increase the activity of bone dissolving cells, they also cause bone forming cells to secrete compounds which attract, increase the numbers and activity of the bone disolving cells as well as keeping them from making the scaffolding onto which bone mineral is laid down. This new understanding may lead to better treatments. Until now they thought only the bone dissolving cells were the culprits.