肥胖和IL-5和GM-CSF变化对乳腺癌转移的影响

Effects of obesity and changes in IL-5 and GM-CSF on breast cancer metastasis

目的:探讨肥胖导致IL-5和GM-CSF变化对小鼠乳腺癌肺转移的影响。方法:20只C57野生型小鼠,随机分为对照组和肥胖组各10只,对照组小鼠采用常规喂养,肥胖组采用高脂肪喂食。模型建立后,在小鼠左后腿注射4T1细胞诱导乳腺癌肺转移模型。检测两组小鼠的乳腺癌肺转移情况、全血IL-5和GM-CSF表达水平及相关肺部炎症指标。结果:两组小鼠乳腺癌转移率无统计学差异(P>0.05),肥胖组小鼠远端肺转移灶数显著高于对照组(P<0.05)。肥胖组小鼠血液中IL-5和GM-CSF的表达显著高于对照组(P<0.05)。GM-CSF表达在全肺显著富集。肥胖组外周血分离的99%的嗜中性粒细胞和68%的单核细胞表达IL-5rα。结论:肥胖导致小鼠的肺中性粒细胞增多,肺中性粒细胞通过以GM-CSF和IL-5依赖的方式增加了乳腺癌转移至肺部的可能性。

Objective:To explore the dynamics of IL-5 and GM-CSF induced by obesity.Methods:C57 female mice were divided into two groups,including the control group and the obesity group.Mice in the control group were fed normally,while those in the obesity group were fed with high fat food.After constructing the model,4T1 cells were injected into the left leg of mice to build the model of lung metastatic breast cancer.The metastasis condition,the expression level of IL-5 and GM-CSF in whole blood and the lung associated inflammation indexes were measured and compared between two groups.Results:No significantly different ratio of lung metastasis was observed between two groups(P>0.05).The expression level of IL-5 and GM-CSF was much higher in the obesity group than in the control group(P<0.05).GM-CSF were abundant in lung.99%of polymorphonuclear neutrophils and 68%of monocyte,isolated from peripheral blood of mice in the obesity group,expressed IL-5rα.And obesity could induce an increase of IL-5rα+monocyte in blood and lung.Conclusion:Obesity could induce the abundance of neutrophil granulocyte in lung of mice,and neutrophil could increase the risk of lung metastasis in breast cancer through GM-CS and IL-5 dependent methods.