Parathyroid hormone-related protein (PTHRP) is responsible for production of bone metastasis, but not visceral metastasis, by human small cell lung cancer SBC-5 cells in natural killer cell-depleted SCID mice
Parathyroid hormone-related protein (PTHRP) is responsible for production of bone metastasis, but not visceral metastasis, by human small cell lung cancer SBC-5 cells in natural killer cell-depleted SCID mice
复制标题
DOI：
10.1002/ijc.11586
复制
发表时间：
2004-02-10
影响因子：
6.4
通讯作者：
Sone, S
中科院分区：
文献类型：
--
作者：
Miki, T;Yano, S;Sone, S
我们之前使用高度表达甲状旁腺激素相关蛋白（PTHrP）的人小细胞肺癌细胞（SBC-5）在自然杀伤（NK）细胞耗尽的严重联合免疫缺陷（SCID）小鼠中建立了溶骨性骨转移模型，该模型具有多器官播散。在我们目前的研究中，我们使用抗 PTHrP 中和抗体 (Ab) 评估了 PTHrP 对 SBC-5 细胞骨转移的作用。抗PTHrP Ab不影响体外SBC-5细胞的增殖或细胞因子产生。重复静脉注射抗PTHrP抗体以剂量依赖的方式抑制骨转移的形成，而相同的治疗对内脏器官（肺、肝、肾和淋巴结）的转移没有显着影响。此外，抗PTHrP Ab治疗改善了升高的血清钙水平，这与抑制溶骨性骨转移有关，表明抗PTHrP Ab可能通过中和PTHrP来抑制骨吸收，从而抑制骨转移。这些发现表明，PTHrP 对于小细胞肺癌 SBC-5 细胞的骨转移至关重要，但不是内脏转移。 (C) 2003 Wiley-Liss, Inc.
We previously established an osteolytic bone metastasis model with multiorgan dissemination in natural killer (NK) cell-depleted severe combined immunodeficient (SCID) mice using human small cell lung cancer cells (SBC-5), which highly express the parathyroid hormone-related protein (PTHrP). In our present study, we evaluated the role of PTHrP on bone metastasis by SBC-5 cells using anti-PTHrP neutralizing antibody (Ab). Anti-PTHrP Ab did not affect the proliferation or cytokine production of SBC-5 cells in vitro. Repeated intravenous injection with anti-PTHrP Ab inhibited the formation of bone metastasis in a dose-dependent manner, while the same treatment had no significant effect on the metastasis to visceral organs (lung, liver, kidney and lymph node). In addition, treatment with anti-PTHrP Ab improved the elevated serum calcium level, associated with inhibition of osteolytic bone metastasis, suggesting that anti-PTHrP Ab inhibited bone metastasis via suppression of bone resorption probably by neutralizing PTHrP. These findings suggest that PTHrP is essential for bone metastasis, but not visceral metastasis, by small cell lung cancer SBC-5 cells. (C) 2003 Wiley-Liss, Inc.