The effect of cigarette smoke exposure on pulmonary metastatic disease in a murine model of metastatic breast cancer
The effect of cigarette smoke exposure on pulmonary metastatic disease in a murine model of metastatic breast cancer
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DOI：
10.1378/chest.125.4.1467
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发表时间：
2004-04-01
期刊：
影响因子：
9.6
通讯作者：
Erickson, K
中科院分区：
文献类型：
--
作者：
Murin, S;Pinkerton, KE;Erickson, K
简介：吸烟的女性比不吸烟的女性患致命性乳腺癌的几率更高。流行病学研究表明，吸烟与乳腺癌肺转移之间存在关联。研究目的：在转移性乳腺癌小鼠模型中检查暴露于香烟烟雾与肺转移之间的关系。研究设计：前瞻性随机研究。设置：动物研究实验室。实验对象：雌性性成熟BALB/cAnN小鼠。干预措施：将小鼠随机分为实验组和对照组。实验动物在专门的暴露室中暴露于香烟烟雾，浓度选择为接近主动吸烟。对照动物暴露于过滤空气。暴露开始后一周，将小鼠乳腺肿瘤细胞（肿瘤细胞系4526）以三种浓度（50，000、100，000或150，000个细胞/100穆尔）之一注射到实验动物的尾静脉中。结果：在每种细胞注射浓度下，暴露于烟雾的动物肺中的平均转移负荷始终更大（在50，000个细胞/100穆尔时，分别为9.8对4.8 μ m（3）[p <0.01];在100，000个细胞/100穆尔时，分别为34.5对17.4 μ m（3）[p <0.10];和在150，000个细胞/100穆尔时，分别为54.0和31.5 μ m（3）[p <0.05]）。这在很大程度上是由于每只动物的转移性结节数量显著增加（50，000个细胞/100穆尔，分别为8.7对4.8 [p <0.001]; 100，000个细胞/100穆尔，分别为24.3对14.0 [p> 0.10];而在每100穆尔150，000个细胞时，分别为42.0和20.1 [p <0.02]），而不是结节大小的变化。结论：在转移性乳腺细胞癌的小鼠模型中，香烟烟雾暴露与总肺转移负荷的增加有关。这项研究为吸烟对转移过程的不利影响提供了实验支持，并提出了吸烟者增加乳腺癌死亡率的可能机制。
Introduction: Women who smoke have a higher rate of fatal breast cancer than nonsmoking women. An association between smoking and pulmonary metastases from breast cancer has been suggested by epidemiologic studies.Study objectives: To examine the relationship between exposure to cigarette smoke and pulmonary metastasis in a murine model of metastatic mammary cancer.Study design: Prospective, randomized study.Setting: Animal research laboratory.Experimental subjects: Female sexually mature BALB/cAnN mice.Interventions: Mice were randomly divided into experimental and control groups. Experimental animals were exposed to cigarette smoke in specialized exposure chambers, at concentrations chosen to approximate active cigarette smoking. Control animals were exposed to filtered air. One week after the initiation of exposures, mouse mammary tumor cells (tumor cell line 4526) were injected into the tail veins of experimental animals at one of three concentrations (50,000, 100,000, or 150,000 cells per 100 muL). Three weeks later, the mice were killed, and pulmonary metastases were counted and measured.Results: The mean metastatic burden in the lungs was consistently greater for smoke-ex posed animals at each concentration of cells injected (at 50,000 cells per 100 muL, 9.8 vs 4.8 mum(3), respectively [p < 0.01]; at 100,000 cells per 100 muL, 34.5 vs 17.4 mum(3), respectively [p < 0.10]; and at 150,000 cells per 100 muL, 54.0 vs 31.5 mum(3), respectively [p < 0.05]). This was largely attributable to a significant increase in the number of metastatic nodules per animal (at 50,000 cells per 100 muL, 8.7 vs 4.8, respectively [p < 0.001]; at 100,000 cells per 100 muL, 24.3 vs 14.0, respectively [p > 0.10]; and at 150,000 cells per 100 muL, 42.0 vs 20.1, respectively [p < 0.02]) rather than to a change in nodule size.Conclusions: Cigarette smoke exposure is associated with an increase in the total pulmonary metastatic burden in this murine model of metastatic mammary cell cancer. This study provides experimental support for an adverse effect of smoking on the metastatic process and suggests a possible mechanism for smokers' increased breast cancer mortality.