?文章標題：Palmitic acid reprograms neutrophils to compromise vascular integrity and promote breast cancer lung metastasis
作者列表：Peng Qian, Yuxin Li, Yifeng Han, Chun Xu, Peng Zou, Fuming Yang, Xiaozhen Kang, Mengdi Wu, Jie Dong, Zhengyun Zou, Jiwu Wei
影響因子：26.3
期刊：IMMUNITY
發(fā)表時間：2026-4-24
DOI:10.1016/j.immuni.2026.03.026
文獻主題：Highlights
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Pre-metastatic lung accumulates palmitic acid during breast cancer progression
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Neutrophil-derived lipocalin-2 impairs pulmonary endothelial integrity
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Palmitic acid induces lipocalin-2 release through the TLR4-NF-κB signaling pathway
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Targeting endothelial fatty acid synthesis reduces breast cancer lung metastasis
Summary
Pre-metastatic niche formation in the lung creates a permissive microenvironment for breast cancer metastasis, characterized by metabolic reprogramming of resident cells, recruitment of suppressive neutrophils, and vascular remodeling. However, the role of lipids in regulating neutrophil-endothelial interactions, particularly in facilitating tumor cell extravasation, remains largely undefined. Here, we showed that triple-negative breast cancer established a palmitic acid-enriched lung microenvironment that drove tumor cell extravasation and colonization. Pulmonary endothelial cells were a major source of palmitic acid, which activated neutrophils to produce lipocalin-2 (LCN2) via the Toll-like receptor 4 (TLR4)-NF-κB pathway. Neutrophil-derived LCN2 disrupted endothelial tight junctions, compromised vascular integrity, and facilitated tumor cell extravasation. Targeting endothelial fatty acid synthesis using glucagon-like peptide-1 receptor agonists preserved vascular integrity and suppressed lung metastasis. These findings uncover a lipid-driven mechanism underlying metastatic organotropism and highlight metabolic intervention as a potential therapeutic strategy against breast cancer lung metastasis.