Zhu Yong-Yun, Zhao Ying-Chun, Chen Chuang, Xie Min
Department of Thyroid and Breast Surgery, Wuhu Second People's Hospital, China.
Department of Thyroid and Breast Surgery, Wuhu Traditional Chinese Medicine Hospital, China.
Gene. 2022 Feb 20;812:146100. doi: 10.1016/j.gene.2021.146100. Epub 2021 Dec 2.
In humans, breast cancer affects a large number of females and causes a high rate of mortality worldwide. Chemokine (C-C motif) ligand 5 (CCL5) is one of the cytokines that is highly correlated to the invasive and metastatic stages of breast cancer. Our previous study has suggested the prognostic value of CCL5 expression in luminal B (HER2 - ) breast cancer. In this study, CCL5 expression was upregulated or knockdown in a luminal B breast cancer cell line, ZR7530. Further, we elucidated the effects of CCL5 on the differentiation of THP-1 monocytes into M2 macrophages. Overexpression of CCL5 affected THP-1-M2 differentiation and phosphorylation of MEK1/2, ERK1/2, and STAT2 in the cocultivated cell lines. We report that the knockdown of CCR5, a receptor of CCL5 in THP-1, inhibited the effect of ZR7530 in promoting THP-1-M2 differentiation. Furthermore, our data revealed that the inhibition of MEK1/2 and STAT3 in THP-1 cells produced equivalent results similar to those of CCL5 knockdown. In summary, we revealed the role of CCL5 in the polarization of M2 macrophages. Furthermore, we studied its interaction with CCR5 and MEK/STAT3 signaling members. These targets could be used as key regulatory members in human breast cancer therapy.
在人类中，乳腺癌影响着大量女性，并且在全球范围内导致高死亡率。趋化因子（C-C基序）配体5（CCL5）是与乳腺癌侵袭和转移阶段高度相关的细胞因子之一。我们之前的研究表明CCL5表达在腔面B（HER2-）型乳腺癌中具有预后价值。在本研究中，在腔面B型乳腺癌细胞系ZR7530中上调或敲低CCL5表达。此外，我们阐明了CCL5对THP-1单核细胞分化为M2巨噬细胞的影响。CCL5的过表达影响了共培养细胞系中THP-1向M2的分化以及MEK1/2、ERK1/2和STAT2的磷酸化。我们报道，敲低THP-1中CCL5的受体CCR5可抑制ZR7530促进THP-1向M2分化的作用。此外，我们的数据显示，抑制THP-1细胞中的MEK1/2和STAT3产生了与敲低CCL5类似的结果。总之，我们揭示了CCL5在M2巨噬细胞极化中的作用。此外，我们研究了其与CCR5以及MEK/STAT3信号成员的相互作用。这些靶点可作为人类乳腺癌治疗中的关键调控成员。
