雌二醇通过上调M-CSF表达促进乳腺癌教化单核细胞

Estradiol May Upregulate M-CSF to Promote Breast Cancer Recruit and Activate Monocytes

目的:研究雌二醇对MCF-7细胞教化单核细胞分化为肿瘤相关巨噬细胞的影响。方法:分别用10 nM雌二醇及10 nM雌二醇+1μM他莫昔芬处理雌激素受体阳性乳腺癌细胞株MCF-7,48 h后收集细胞培养上清,利用细胞因子芯片检测不同处理组单核细胞活化相关蛋白与空白对照组MCP-1及M-CSF的表达差异,利用细胞Transwell niche检测其对单核细胞活化功能的影响。结果:Bio-Rad细胞因子芯片检测发现空白对照组、雌二醇组及雌二醇+他莫昔芬组细胞上清中CSF1浓度分别为(1.83±0.18),(29.71±8.06)及(10.90±2.38)pg/m L,MCP-1分别为(31.33±2.40),(75.37±5.50)和(41.97±5.80)pg/m L,比较差异均有统计学意义(P<0.05)。雌二醇处理组CD163的mRNA水平是对照组(76.83±12.80)倍,他莫昔芬加雌二醇组是对照组的(6.5±1.71)倍,比较差异有统计学意义(F=96,P<0.01)。对照组、雌二醇处理组及他莫昔芬加雌二醇处理组每个高倍镜视野内U937细胞数目分别为(28±6)、(188±16)及(82±9)个,比较差异有统计学意义(F=160,P<0.05)。结论:雌二醇通过上调激素依赖型乳腺癌细胞株MCF-7表达M-CSF从而增强其对单核细胞的教化,而他莫昔芬可部分阻断其发挥效应。

Objective:To investigate the effect of Estradiol on educating monocyte differentiation into tumor associated macrophage in MCF-7 coculture system.Method:48 h after treated with 10 nM Estradiol or 10 nM Estradiol+1μM Tamoxifen,MCP-1 and M-CSF in human breast cancer cell line MCF-7 culture supernatant were detected,they were given Transwell niche to further explore their effects on the recruitment and activation of monocyte.Result:Bio-Rad cytokine chip assay showed that the M-CSF concentration in the supernatant of blank control group,Estradiol group and Estradiol+Tamoxifen group were(1.83±0.18),(29.71±8.06)and(10.90±2.38)pg/mL,and the MCP-1 concentration were(31.33±2.40),(75.37±5.50)and(41.97±5.80)pg/mL respectively,the differences were statistically significant(P<0.05).The level of CD163 mRNA in estradiol treatment group was(76.83±12.80)times higher than that in control group,and that in Estradiol+Tamoxifen group was(6.50±1.71)times higher than that in control group(F=96,P<0.01).The number of U937 cells in the control group,the Estradiol treatment group and the Estradiol+Tamoxifen treatment group were(28±6),(188±16)and(82±9)respectively,the difference was statistically significant(F=160,P<0.05).Conclusion:Estradiol may promote hormone dependent breast cancer cell lines MCF-7 to secrete MCP-1 and M-CSF,thereby educate monocyte differentiation into tumor associated macrophage,while Tamoxifen may partially block the effect.