CCL8 Promotes Postpartum Breast Cancer by Recruiting M2 Macrophages
CCL8 Promotes Postpartum Breast Cancer by Recruiting M2 Macrophages
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DOI：
10.1016/j.isci.2020.101217
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发表时间：
2020-06-26
期刊：
影响因子：
5.8
通讯作者：
Kiaris, Hippokratis
中科院分区：
文献类型：
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作者：
Farmaki, Elena;Kaza, Vimala;Kiaris, Hippokratis
在动物模型中，产后乳腺的微环境促进了肿瘤的生长和转移，并与乳腺癌风险增加和患者的不良疾病结局有关。我们以前的研究表明，趋化因子CCL8通过调节肿瘤微环境的促肿瘤活性而参与乳腺癌的转移。在此，我们发现CCL8在乳腺退行性变过程中高表达，并在退化期第二阶段促进M2亚型巨噬细胞的渗透。对CCl8缺陷动物的癌细胞接种研究表明，CCl8在退化过程中会加速SET上的肿瘤，但在未分娩的动物中不会。巨噬细胞的耗竭消除了CCL8在消退过程中的促肿瘤作用，提示CCL8通过募集巨噬细胞而促进肿瘤生长。这些结果强调了CCL8在产后乳腺癌发生发展中的作用，并提示了靶向CCL8在疾病管理中的潜在价值。
The microenvironment of postpartum mammary gland promotes tumor growth and metastasis in animal models and is linked to increased risk of breast cancer and poor disease outcome in patients. Our previous studies showed the involvement of the chemokine CCL8 in breast cancer metastasis through modulation of the tumor-promoting activity of the tumor microenvironment. Here we show that CCL8 is highly expressed during mammary gland involution and enhances the infiltration of M2 subtype macrophages at the second phase of involution. Cancer cell inoculation studies in Ccl8-deficient animals indicate that CCL8 accelerates tumor on set during involution but not in nulliparous animals. Depletion of macrophages abolished the tumor-promoting effect of CCL8 in involution suggesting the specific role of CCL8 in promoting tumor growth by recruiting macrophages.These results underscore the role of CCL8 in the development of postpartum breast cancer and suggest the potential value of targeting CCL8 in disease management.