Breast cancer (BC) is one of the most common types of cancer in women in the United Arab Emirates. Immunogenic tumours, such as triple-negative breast cancer (TNBC), show increased neutrophil infiltration, which is associated with poor prognosis and limited efficacy of immunotherapy. This study aims to investigate in vitro the bidirectional effect of neutrophils on metastatic TNBC (MDA-MB-231) compared to less-metastatic luminal breast cancer (MCF-7) cell lines. We found that BC cells or their conditioned medium (CM) reduced the viability of neutrophil-like cells (HL60). This was supported by increased cellular stress and NETosis in differentiated HL60 cells (dHL60) upon exposure to MDA-MB-231 compared to MCF-7-CM using nucleic acid staining essays. Flow cytometry showed comparable expression of inflammatory markers by polymorphonuclear cells (PMN) when treated with MDA-MB-231-CM and standard polarizing cocktails. Furthermore, MDA-MB-231-CM triggered an inflammatory pattern with evidence of stronger adhesion (CD62L) and degranulation (CD11b and CD66b) phenotypes. The proinflammatory polarization of dHL60 by MDA-MB-231-CM was additionally confirmed by the elevated CD54 expression, myeloperoxidase, and CD11b protein levels, which matched an increased transwell migratory capacity. In conclusion, BC might use neutrophils to their benefit through NETosis and complement system activation, which makes this crosstalk a potential mechanism for understanding tumour progression.
乳腺癌是阿联酋女性最常见的恶性肿瘤之一。在三阴性乳腺癌等免疫原性肿瘤中，中性粒细胞浸润增加与不良预后及免疫疗法疗效受限密切相关。本研究旨在体外比较中性粒细胞对高转移性三阴性乳腺癌细胞系（MDA-MB-231）与低转移性管腔型乳腺癌细胞系（MCF-7）的双向调控作用。研究发现，乳腺癌细胞及其条件培养基可降低中性粒细胞样细胞（HL60）的存活率。核酸染色实验进一步证实，与MCF-7条件培养基相比，MDA-MB-231条件培养基能显著增强分化HL60细胞的应激反应并诱发NETosis现象。流式细胞术显示，经MDA-MB-231条件培养基与标准极化诱导剂处理的多形核白细胞具有相似的炎症标志物表达谱。值得注意的是，MDA-MB-231条件培养基可诱导更强的炎症表型，表现为黏附分子（CD62L）表达增强及脱颗粒标志物（CD11b与CD66b）显著上调。CD54表达升高、髓过氧化物酶活性增强及CD11b蛋白水平上升进一步证实了MDA-MB-231条件培养基对分化HL60细胞的促炎极化作用，这种极化状态与其增强的Transwell迁移能力相吻合。综上，乳腺癌可能通过激活NETosis及补体系统途径调控中性粒细胞功能，这种细胞间相互作用为理解肿瘤进展机制提供了新视角。
Characterizing the Inflammatory Profile of Neutrophil-Rich Triple-Negative Breast Cancer
肿瘤(癌症)患者之家