NF-κB in breast cancer cells promotes osteolytic bone metastasis by inducing osteoclastogenesis via GM-CSF
NF-κB in breast cancer cells promotes osteolytic bone metastasis by inducing osteoclastogenesis via GM-CSF
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DOI：
10.1038/nm1519
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发表时间：
2007-01-01
期刊：
影响因子：
82.9
通讯作者：
Wang, Cun-Yu
中科院分区：
文献类型：
--
作者：
Park, Bae Keun;Zhang, Honglai;Wang, Cun-Yu
晚期乳腺癌经常转移到骨，导致溶骨病变，但其潜在机制尚不清楚。在这里，我们报道核因子- κ B （nf - κ B）通过刺激破骨细胞的发生在乳腺癌的溶骨转移中起关键作用。通过体内骨转移模型，我们发现乳腺癌细胞中组成性nf - κ B活性对骨溶解性骨转移的骨吸收特征至关重要。我们发现编码粒细胞巨噬细胞集落刺激因子（GM-CSF）的基因是NF-kappa B的关键靶点，并发现它通过刺激破骨细胞的发育介导乳腺癌的溶骨转移。此外，我们观察到GM-CSF的表达与乳腺癌患者骨转移肿瘤组织中NF-kappa B的激活相关。这些结果揭示了NF-kappa B通过GM-CSF诱导在溶骨性骨转移中的新的特异性作用，提示NF-kappa B是治疗乳腺癌和预防骨转移的潜在靶点。
Advanced breast cancers frequently metastasize to bone, resulting in osteolytic lesions, yet the underlying mechanisms are poorly understood. Here we report that nuclear factor-kappa B (NF-kappa 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-kappa 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-kappa 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-kappa B activation in bone-metastatic tumor tissues from individuals with breast cancer. These results uncover a new and specific role of NF-kappa B in osteolytic bone metastasis through GM-CSF induction, suggesting that NF-kappa B is a potential target for the treatment of breast cancer and the prevention of skeletal metastasis.