Zhang Xiwei, Li Guoqing, Chen Tieyan, Sun Haohang, Dai Ji, Chen Qi, Chen Mengze, Yan Meidi
Department of General Surgery, Zhenhai District People's Hospital, No. 718, South 2nd West Road, Camel Street, Zhenhai District, Ningbo City, 315200, Zhejiang, China.
J Cancer Res Clin Oncol. 2025 May 14;151(5):163. doi: 10.1007/s00432-025-06191-0.
Among the various types of breast cancer that endanger women's lives, triple-negative breast cancer (TNBC) stands out due to its extreme heterogeneity, aggressive nature, and high likelihood of recurrence. The absence of unique targets and targeted drugs is a major factor contributing to the failure of cancer treatments and the eventual death of patients.
Single-cell RNA sequencing (scRNA-seq) was applied to investigate the immune microenvironment of TNBC, facilitating the detection of key cell subpopulations and regulatory genes. The mRNA expression of SLC31A1 in macrophages was measured by qPCR. Flow cytometry was utilized to ascertain the M2 macrophage proportion and cancer cell apoptosis. Transwell and scratch assays were conducted to gauge cancer cell migration and invasion. Copper ion and HO detection kits were employed to evaluate the copper ion content and oxidative stress levels in macrophages.
SLC31A1 overexpression in TNBC myeloid cells, particularly macrophage subpopulations, was identified through scRNA-seq analysis. Cluster and pseudotime analyses showed that macrophages with high SLC31A1 expression are often in advanced stages of cell growth, accompanied by notable changes in oxidative stress. Functional studies revealed that knocking down SLC31A1 in macrophages significantly reduced M2-type polarization. The conditioned medium from these macrophages markedly inhibited TNBC cell migration and invasion, while promoting apoptosis. Furthermore, SLC31A1 knockdown resulted in decreased copper ion content and HO levels in macrophages.
SLC31A1 enhances the malignant phenotype of TNBC cells by inducing M2 polarization in macrophages.
在危及女性生命的各类乳腺癌中，三阴性乳腺癌（TNBC）因其极端的异质性、侵袭性本质以及高复发可能性而格外突出。缺乏独特靶点和靶向药物是导致癌症治疗失败及患者最终死亡的主要因素。
应用单细胞RNA测序（scRNA-seq）来研究TNBC的免疫微环境，以促进关键细胞亚群和调控基因的检测。通过qPCR检测巨噬细胞中SLC31A1的mRNA表达。利用流式细胞术确定M2巨噬细胞比例和癌细胞凋亡情况。进行Transwell和划痕试验以评估癌细胞的迁移和侵袭能力。使用铜离子和HO检测试剂盒评估巨噬细胞中的铜离子含量和氧化应激水平。
通过scRNA-seq分析确定TNBC髓系细胞中，尤其是巨噬细胞亚群中SLC31A1过表达。聚类和拟时间分析表明，高表达SLC31A1的巨噬细胞通常处于细胞生长的晚期阶段，同时伴有氧化应激的显著变化。功能研究表明，敲低巨噬细胞中的SLC31A1可显著降低M2型极化。这些巨噬细胞的条件培养基显著抑制TNBC细胞的迁移和侵袭，同时促进细胞凋亡。此外，敲低SLC31A1导致巨噬细胞中铜离子含量和HO水平降低。
SLC31A1通过诱导巨噬细胞的M2极化增强TNBC细胞的恶性表型。
