文章摘要

Mcemp1对三阴性乳腺癌中肿瘤相关巨噬细胞极化状态、增殖及凋亡的影响

作者: 1白钰明, 1,2云芬, 1,2施琳, 1,2贾永峰, 1,2刘霞
1 内蒙古医科大学基础医学院，呼和浩特 010000
2 内蒙古医科大学附属医院病理科，呼和浩特 010000
通讯: 刘霞 Email: 964889319@qq.com
DOI: 10.3978/j.issn.2095-6959.2022.11.001
基金: 内蒙古自治区应用技术研究与开发项目(2019GG083)。

摘要

目的：研究肥大细胞表达膜蛋白1(mast cell expressed membrane protein 1，Mcemp1)对三阴性乳腺癌(triple-negative breast cancer，TNBC)中肿瘤相关巨噬细胞(tumor-associated macrophages，TAMs)极化状态、增殖及凋亡的影响。方法：生物学信息分析Mcemp1与肿瘤浸润免疫细胞相关性。构建鼠源性TAMs模型。Real-time RT-PCR验证TAMs模型，并检测沉默Mcemp1后对TAMs极化状态的影响。活细胞计数法检测沉默Mcemp1对TAMs增殖的影响。流式细胞术检测沉默Mcemp1对TAMs细胞周期及凋亡的影响。结果：在乳腺癌中Mcemp1的表达与M0型巨噬细胞浸润呈正相关(P<0.05)。与单核巨噬细胞RW264.7相比，TAMs中CD206、IL-10的表达均显著升高(均P<0.05)，IL-6、TNF的表达均显著下降(均P<0.05)。沉默Mcemp1的TAMs中IL-6、CXCL9、CXCL10、IL-10、CD86和TNF的表达均显著上调(均P0.05)，在第3、4天时增多(均P<0.05)。沉默Mcemp1使得TAMs的S期延长，G2/M期缩短(P<0.05)。沉默Mcemp1的TAMs凋亡率显著下降(P<0.05)。结论：Mcemp1在TNBC中TAMs具有免疫抑制的作用，下调其在TAMs的表达水平，可促进增殖并同时抑制细胞凋亡。
关键词： 肥大细胞表达膜蛋白1；肿瘤相关巨噬细胞；极化；增殖；三阴性乳腺癌

Influence of Mcemp1 on polarization status, proliferation, and apoptosis of tumor-associated macrophages in triple-negative breast cancer

Authors: 1BAI Yuming, 1,2YUN Fen, 1,2SHI Lin, 1,2JIA Yongfeng, 1,2LIU Xia
1 Basic Medical College, Inner Mongolia Medical University, Hohhot 010000, China
2 Department of Pathology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010000, China

CorrespondingAuthor: LIU Xia Email: 964889319@qq.com

DOI: 10.3978/j.issn.2095-6959.2022.11.001

Foundation: This work was supported by the Inner Mongolia Autonomous Region Applied Technology Research and Development Project, China (2019GG083).

Abstract

Objective: To investigate the effect of mast cell expressed membrane protein 1 (Mcemp1) on the polarization status, proliferation, and apoptosis of tumor-associated macrophages (TAMs) in triple-negative breast cancer (TNBC). Methods: Biological information analysis of Mcemp1 correlation with tumor-infiltrating immune cells. Construction of murine-derived TAMs model. Real-time RT-PCR was used to validate the TAMs model and to detect the effect on the polarization state of TAMs after silencing Mcemp1. Live cell counting assay was used to detect the effect of silencing Mcemp1 on the proliferation of TAMs. Flow cytometry was used to detect the effect of silencing Mcemp1 on the cell cycle of TAMs as well as apoptosis. Results: The expression of Mcemp1 in breast cancer was positively correlated with M0-type macrophage infiltration (P<0.05). The expression of CD206 and IL-10 was significantly higher in TAMs (both P<0.05) and the expression of IL-6 and TNF was significantly lower in TAMs (both P<0.05) compared with normal RW264.7 cells. The expression of IL-6, CXCL9, CXCL10, IL-10, CD86, and TNF was significantly upregulated in TAMs with Mcemp1 silencing (all P<0.05). The number of cells in TAMs with Mcemp1 silencing did not change significantly at the 1st and 2nd day (both P>0.05) and increased at the 3rd and 4th day (both P<0.05). Silencing Mcemp1 prolonged the S phase and shortened the G2/M phase of TAMs (P<0.05). The apoptosis rate of TAMs silenced by Mcemp1 was significantly decreased (P<0.05). Conclusion: Mcemp1 has an immunosuppressive effect on TAMs in TNBC, and downregulation of its expression level in TAMs promotes proliferation and simultaneously inhibits apoptosis.

Keywords： mast cell expressed membrane protein 1; tumor-associated macrophages; polarization; proliferation; triple-negative breast cancer

文章选项

下载引文

分享