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Article
Nature Medicine 13, 62 - 69 (2006)
Published online: 10 December 2006 | doi:10.1038/nm1519
NF-
B in breast cancer cells promotes osteolytic bone metastasis by inducing osteoclastogenesis via GM-CSF
Bae Keun Park1, Honglai Zhang1, Qinghua Zeng1, Jinlu Dai2, Evan T Keller2, Thomas Giordano3, Keni Gu4, Veena Shah4, Lei Pei4, Richard J Zarbo4, Laurie McCauley3,5, Songtao Shi6, Shaoqiong Chen1 & Cun-Yu Wang1
Abstract
Advanced breast cancers frequently metastasize to bone, resulting in osteolytic lesions, yet the underlying mechanisms are poorly understood. Here we report that nuclear factor–
B (NF-B) plays a crucial role in the osteolytic bone metastasis of breast cancer by stimulating osteoclastogenesis. Using an in vivo bone metastasis model, we found that constitutive NF-B activity in breast cancer cells is crucial for the bone resorption characteristic of osteolytic bone metastasis. We identified the gene encoding granulocyte macrophage–colony stimulating factor (GM-CSF) as a key target of NF-B and found that it mediates osteolytic bone metastasis of breast cancer by stimulating osteoclast development. Moreover, we observed that the expression of GM-CSF correlated with NF-B activation in bone-metastatic tumor tissues from individuals with breast cancer. These results uncover a new and specific role of NF-B in osteolytic bone metastasis through GM-CSF induction, suggesting that NF-B is a potential target for the treatment of breast cancer and the prevention of skeletal metastasis.
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