A Bone Metastasis Model With Osteolytic and Osteoblastic Properties of Human Lung Cancer ACC-LC-319/bone2 in Natural Killer Cell-Depleted Severe Combined Immunodeficient Mice
A Bone Metastasis Model With Osteolytic and Osteoblastic Properties of Human Lung Cancer ACC-LC-319/bone2 in Natural Killer Cell-Depleted Severe Combined Immunodeficient Mice
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DOI：
10.3727/096504009789745511
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发表时间：
2009-01-01
影响因子：
3.1
通讯作者：
Sone, Saburo
中科院分区：
文献类型：
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作者：
Otsuka, Shinsaku;Hanibuchi, Masaki;Sone, Saburo
肺癌常伴有多器官转移，而骨是肺癌的多发转移部位。肺癌经常发生溶骨性骨转移，较少发生成骨性骨转移。肺癌的溶骨转移模型已有报道，但尚无肺癌的成骨细胞转移模型。在本研究中，我们建立了一个可重复的人类肺癌模型，在自然杀伤细胞耗尽的严重联合免疫缺陷小鼠中具有溶骨性和成骨细胞变化。静脉内接种 ACC-LC-319/bone2 细胞导致小鼠肺、肝和骨中出现转移集落。通过X射线照片依次评估，第28天时观察到溶骨性骨病变，然后在第35天时检测到成骨细胞病变。组织学检查显示存在骨刺，这是成骨细胞骨转移的标志，其中几乎观察不到破骨细胞。使用抗人血管内皮生长因子抗体贝伐珠单抗以及唑来膦酸盐治疗可抑制实验性骨转移的数量，包括 ACC-LC-319/bone2 细胞产生的成骨细胞变化。这些结果表明，我们的 ACC-LC319/bone2 骨转移模型可能有助于了解溶骨性和成骨性转移的分子发病机制，并确定控制肺癌骨转移的分子靶点。
Lung cancer is commonly associated with multiple-organ metastasis, and bone is a frequent metastatic site for lung cancer. Lung cancer frequently develops osteolytic, and less frequently osteoblastic, metastasis to bone. Osteolytic metastasis models of lung cancer have been reported, but no osteoblastic metastasis model is available for lung cancer. In the present study, we established a reproducible model of human lung cancer with both osteolytic and osteoblastic changes in natural killer cell-depleted severe combined immunodeficient mice. Intravenous inoculation of ACC-LC-319/bone2 cells resulted in the development of metastatic colonies in the lung, liver, and bone of the mice. As assessed sequentially by X-ray photographs, osteolytic bone lesions were observed by day 28, and then osteoblastic lesions were detected by day 35. Histological examination revealed the presence of bony spurs, a hallmark of osteoblastic bone metastasis, where osteoclasts were hardly observed. Treatment with an anti-human vascular endothelial growth factor antibody, bevacizumab, as well as zoledronate, inhibited the number of experimental bone metastases, including osteoblastic changes produced by ACC-LC-319/bone2 cells. These results indicate that our bone metastasis model by ACC-LC319/bone2 might be useful to understand the molecular pathogenesis of osteolytic and osteoblastic metastasis, and to identify molecular targets to control bone metastasis of lung cancer.