Metastatic breast cancer induces an osteoblast inflammatory response

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...

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Bibliographic Details
Published in:Experimental cell research 2008, Vol.314 (1), p.173-183
Main Authors: Kinder, Michelle, Chislock, Elizabeth, Bussard, Karen M., Shuman, Laurie, Mastro, Andrea M.
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Bone Neoplasms - immunology
Bone Neoplasms - secondary
Bone Resorption - etiology
Bone Resorption - metabolism
Bone Resorption - physiopathology
Bones
Breast cancer
Breast Neoplasms - immunology
Breast Neoplasms - pathology
Calcification, Physiologic - physiology
Carcinoma - immunology
Carcinoma - secondary
Cell Communication - drug effects
Cell Communication - physiology
Cell Line, Tumor
Cellular biology
Chemokine CCL2 - metabolism
Chemokine CCL2 - secretion
Culture Media, Conditioned - pharmacology
Cytokines - metabolism
Cytokines - secretion
Female
Humans
IL-6
IL-8
Inflammation
Inflammatory diseases
Interleukin-6 - metabolism
Interleukin-6 - secretion
Interleukin-8 - metabolism
Interleukin-8 - secretion
MCP-1
Metastasis
Mice
Neoplasm Metastasis - immunology
Neoplasm Metastasis - physiopathology
Osteitis - etiology
Osteitis - physiopathology
Osteoblasts
Osteoblasts - drug effects
Osteoblasts - metabolism
Osteoblasts - secretion
Osteoclasts - metabolism
Osteogenesis - physiology
Stress, Physiological - etiology
Stress, Physiological - metabolism
Stress, Physiological - physiopathology
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Summary: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.
ISSN:0014-4827
1090-2422
DOI:10.1016/j.yexcr.2007.09.021