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交替活化的巨噬细胞/单核吞噬细胞促进乳腺癌细胞系SKBR3的生长和侵袭

[Alternatively activated macrophages/mononuclear phagocytes promote growth and invasion of breast cancer cell line SKBR3].

作者信息

Guo Ju-jiang, Su Feng-xi, Yao He-rui, Chen Ji-sheng

机构信息

Breast Cancer Center, Second Affiliated Hospital of SunYat-sen University, Guangzhou 510120, China. E-mail:

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2007 Apr;27(4):410-3.

Abstract

OBJECTIVE

To study the effect of alternatively activated macrophages /mononuclear phagocytes(MNP) on breast cancer cells and explore the mechanisms for the action of tumor-associated macrophages in breast cancer.

METHODS

Human peripheral blood monocytes were isolated and cultured in vitro and divided into 3 groups, namely classically activated monocytes (CAM) which were induced by lipopolysaccharide, alternatively activated monocytes (AAM) induce by IL-4, and control cells treated with the culture medium only. After cell culture for 48-72 h, the mRNA of tumor necrosis factor-alpha (TNF-alpha), alternative monocytes activation- associated CC-chemokine 1 (AMAC-1), and beta-actin of the 3 groups were extracted for RT-PCR, or the cells were cocultured with breast cancer cell line SKBR3, or seeded in chicken chorioallantoic membrane along with SKBR3.

RESULTS

TNF-alpha mRNA was significantly increased in CAM, and AMAC-1 was highly expressed in AAM. The coculture experiments showed that CAM exhibited obvious inhibitory effect on SKBR3 cells after a 3-day culture whereas AAM significantly promoted the growth of SKBR3 cells after a 5-day culture. In chicken on chorioallantoic membrane experiment, the macrophages promoted tumor angiogenesis and AAM showed the most obvious effect.

CONCLUSION

IL-4 induces high expression of AMAC-1, a molecular marker of AAM, in the macrophages, and AAM can promote the growth of SKBR3 cells and tumor angiogenesis.

摘要

目的

研究交替活化的巨噬细胞/单核吞噬细胞(MNP)对乳腺癌细胞的作用,并探讨肿瘤相关巨噬细胞在乳腺癌中发挥作用的机制。

方法

分离人外周血单核细胞并进行体外培养,分为3组,即由脂多糖诱导的经典活化单核细胞(CAM)、由白细胞介素-4诱导的交替活化单核细胞(AAM)以及仅用培养基处理的对照细胞。细胞培养48 - 72小时后,提取3组细胞的肿瘤坏死因子-α(TNF-α)、交替单核细胞活化相关CC趋化因子1(AMAC-1)及β-肌动蛋白的mRNA进行逆转录聚合酶链反应(RT-PCR),或将细胞与乳腺癌细胞系SKBR3共培养,或与SKBR3一起接种于鸡胚绒毛尿囊膜。

结果

CAM中TNF-α mRNA显著增加,AAM中AMAC-1高表达。共培养实验显示,培养3天后CAM对SKBR3细胞表现出明显抑制作用,而培养5天后AAM显著促进SKBR3细胞生长。在鸡胚绒毛尿囊膜实验中,巨噬细胞促进肿瘤血管生成,且AAM作用最为明显。

结论

白细胞介素-4诱导巨噬细胞中AAM的分子标志物AMAC-1高表达,且AAM可促进SKBR3细胞生长及肿瘤血管生成。

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