Author: ["Bae Keun Park","Honglai Zhang","Qinghua Zeng","Jinlu Dai","Evan T Keller","Thomas Giordano","Keni Gu","Veena Shah","Lei Pei","Richard J Zarbo","Laurie McCauley","Songtao Shi","Shaoqiong Chen","Cun-Yu Wang"]
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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–κB (NF-κB) 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-κB 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-κB 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-κB activation in bone-metastatic tumor tissues from individuals with breast cancer. These results uncover a new and specific role of NF-κB in osteolytic bone metastasis through GM-CSF induction, suggesting that NF-κB is a potential target for the treatment of breast cancer and the prevention of skeletal metastasis.Cite this article
Park, B., Zhang, H., Zeng, Q. et al. NF-κB in breast cancer cells promotes osteolytic bone metastasis by inducing osteoclastogenesis via GM-CSF. Nat Med 13, 62–69 (2007). https://doi.org/10.1038/nm1519 