Young women represent a target of E-cigarette (E-cig) companies, raising concern for potential connections with breast cancer (BC) that have not yet been elucidated. We hypothesized that E-cig promotes BC development and lung metastasis possibly through BC-monocyte/tumor-associated macrophage (TAM) crosstalk via CCL5 and V-CAM-1 axes. We demonstrated that E-cig promoted the infiltration of circulating monocytes in mammary fat pad (MFP) model. Furthermore, E-cig exposure significantly enhanced BC cell growth in MFP tumor and metastatic lung colonization; immunohistochemical stains illustrated the increase of TAMs infiltration, reduced BC cell apoptosis and increased proliferation index after E-cig exposure. In vitro studies show E-cig vapor condensate (EVC) treatment upregulated protein expressions of CCL5, V-CAM-1, and other pro-tumorigenic factors in BC cells. Mechanistically, co-culture system demonstrated both EVC and macrophages independently stimulated BC cell growth and the migration via CCL5/CCR1/CCR5 axis. During metastasis, E-Cig exposure stimulated BC cell survival via direct interaction with infiltrated macrophages, regulated by VCAM-1 and integrin α₄β1. Our findings, for the first time, showed that E-cig promotes BC growth and metastasis. This study highlights the critical role of TAMs via CCL5 and VCAM-1 pathways in E-cig promoted BC tumor development.

年轻女性是电子烟（E-cig）公司的目标群体，这引发了人们对尚未阐明的与乳腺癌（BC）潜在联系的担忧。我们假设电子烟可能通过 CCL5 和 V-CAM-1 轴的 BC-单核细胞/肿瘤相关巨噬细胞 (TAM) 串扰来促进 BC 发展和肺转移。我们证明电子烟促进乳腺脂肪垫（MFP）模型中循环单核细胞的浸润。此外，电子烟暴露显着增强了 MFP 肿瘤中 BC 细胞的生长和转移性肺定植；免疫组织化学染色显示，接触电子烟后，TAM 浸润增加，BC 细胞凋亡减少，增殖指数增加。体外研究表明，电子烟蒸汽冷凝物 (EVC) 处理上调了 BC 细胞中 CCL5、V-CAM-1 和其他促肿瘤因子的蛋白表达。从机制上讲，共培养系统证明 EVC 和巨噬细胞独立刺激 BC 细胞生长和通过 CCL5/CCR1/CCR5 轴的迁移。在转移过程中，电子烟暴露通过与受 VCAM-1 和整合素 α ₄ β1 调节的浸润巨噬细胞的直接相互作用刺激 BC 细胞存活。我们的研究结果首次表明电子烟促进乳腺癌的生长和转移。这项研究强调了 TAM 通过 CCL5 和 VCAM-1 通路在电子烟促进 BC 肿瘤发展中的关键作用。