Gender difference in bone metastasis of human small cell lung cancer, SBC-5 cells in natural killer-cell depleted severe combined immunodeficient mice
Gender difference in bone metastasis of human small cell lung cancer, SBC-5 cells in natural killer-cell depleted severe combined immunodeficient mice
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DOI：
10.1007/s10585-010-9333-0
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发表时间：
2010-05
影响因子：
4
通讯作者：
Satoshi Sakaguchi;H. Goto;M. Hanibuchi;Shinsaku Otsuka;H. Ogino;S. Kakiuchi;H. Uehara;S. Yano;Y. Nishioka;S. Sone
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文献类型：
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作者：
Satoshi Sakaguchi;H. Goto;M. Hanibuchi;Shinsaku Otsuka;H. Ogino;S. Kakiuchi;H. Uehara;S. Yano;Y. Nishioka;S. Sone
肺癌经常发生多器官转移，这使得该疾病成为全世界恶性肿瘤相关死亡的主要原因。据报道，性别差异会影响肺癌的发病率和死亡率；然而，性别差异是否以及如何参与肺癌转移尚不清楚。本研究通过使用自然杀伤细胞耗尽的严重联合免疫缺陷小鼠评估了人小细胞肺癌 (SBC-5) 细胞多器官转移的性别差异。在多器官转移中，与雄性小鼠相比，仅雌性小鼠的骨转移形成显着增加，而肝和肺的转移没有观察到显着差异。通过阉割或雄激素受体拮抗剂治疗雄性小鼠来抑制雄激素也导致骨转移显着增加。雌性小鼠和雄激素抑制小鼠骨转移病灶中的破骨细胞数量多于对照雄性小鼠。然而，与性别或雄激素抑制相关的甲状旁腺激素相关蛋白（PTHrP）血清浓度没有显着差异。一项体外研究还表明，性类固醇治疗对 SBC-5 细胞的增殖或 PTHrP 产生没有影响。这些结果表明，性类固醇的平衡在小细胞肺癌骨转移的形成中起着重要作用，并提示骨微环境中癌细胞与宿主细胞之间相互作用的多种机制。
Lung cancer frequently develops multiple organ metastases, which thus makes this disease a leading cause of malignancy-related death worldwide. A gender difference is reported to affect the incidence and mortality of lung cancer; however, whether and how the gender difference is involved in lung cancer metastasis is unclear. This study evaluated the gender difference in multiple organ metastases in human small cell lung cancer (SBC-5) cells by using natural killer cell-depleted severe combined immunodeficient mice. Among multiple organ metastases, only bone metastasis formation significantly increased in female mice in comparison to males, while no significant difference was observed in the metastases to the liver and lungs. The suppression of androgen by castration or androgen receptor antagonist treatment in male mice also induced a significant increase of bone metastases. The number of osteoclasts in the bone metastatic lesions was greater in female mice and in mice with androgen suppression than in control male. However, there was no significant difference in the serum concentration of parathyroid hormone-related protein (PTHrP) associated with gender or androgen suppression. An in vitro study also indicated that sex steroid treatment had no effect on the proliferation or PTHrP production in SBC-5 cells. These results indicate that the balance of sex steroids therefore plays an important role in the formation of bone metastasis in small cell lung cancer, and suggests diverse mechanisms of interaction between cancer cells and host cells in the bone microenvironment.