Lung cancer frequently metastasizes to the bones. An in vivo model is urgently required to identify potential therapeutic targets for the prevention and treatment of lung cancer with bone metastasis. We established a lung adenocarcinoma cell subline (H322L-BO4) that specifically showed metastasis to the leg bones and adrenal glands. This was achieved by repeated isolation of metastatic cells from the leg bones of mice. The cells were intracardially injected into nude mice. Survival was prolonged for mice that received H322L-BO4 cells versus original cells (H322L). H322L-BO4 cells did not exhibit obvious changes in general in vitro properties associated with the metastatic potential (e.g., cell growth, migration, and invasion) compared with H322L cells. However, the phosphorylation of chromosome 9 open reading frame 10/oxidative stress-associated Src activator (C9orf10/Ossa) was increased in H322L-BO4 cells. This result confirmed the increased anchorage independence through C9orf10/Ossa-mediated activation of Src family tyrosine kinase. Reduction of C9orf10/Ossa by shRNA reduced cells' metastasis to the leg bone and prolonged survival in mice. These findings indicate that H322L-BO4 cells can be used to evaluate the effect of candidate therapeutic targets against bone metastatic lung cancer cells. Moreover, C9orf10/Ossa may be a useful target for treatment of lung cancer with bone metastasis.

中文翻译：

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C9orf10/Ossa 调节小鼠模型中已建立的肺腺癌细胞亚系 H322L-BO4 的骨转移

肺癌经常转移至骨骼。迫切需要体内模型来确定预防和治疗骨转移肺癌的潜在治疗靶点。我们建立了一个肺腺癌细胞亚系（H322L-BO4），该亚系特异性地表现出向腿骨和肾上腺的转移。这是通过从小鼠腿骨中反复分离转移细胞来实现的。将细胞心内注射到裸鼠体内。与原始细胞 (H322L) 相比，接受 H322L-BO4 细胞的小鼠的存活时间延长。与H322L细胞相比，H322L-BO4细胞在与转移潜能（例如细胞生长、迁移和侵袭）相关的一般体外特性方面没有表现出明显的变化。然而，H322L-BO4 细胞中 9 号染色体开放阅读框 10/氧化应激相关 Src 激活剂 (C9orf10/Ossa) 的磷酸化增加。这一结果证实了通过 C9orf10/Ossa 介导的 Src 家族酪氨酸激酶激活增加了锚定独立性。 shRNA 减少 C9orf10/Ossa 可减少细胞向腿骨的转移，并延长小鼠的存活时间。这些发现表明H322L-BO4细胞可用于评估候选治疗靶点对骨转移性肺癌细胞的效果。此外，C9orf10/Ossa可能是治疗骨转移肺癌的有用靶点。