Neutrophil extracellular traps (NETs) have been implicated in many cancers, but the regulatory mechanisms in the context of breast cancer have not been thoroughly discussed. This study proposed a mechanism based on collagen-activated DDR1/CXCL5 for NET formation in breast cancer. Through TCGA and GEO-based bioinformatics analysis, we examined the DDR1 expression and the correlation of CXCL5 with immune cell infiltration in breast cancer. It was found that high DDR1 expression was correlated with poor prognosis of patients with breast cancer, and CXCL5 was positively correlated with neutrophil and Treg infiltration. Expression of DDR1 and CXCL5 was determined in collagen-treated breast cancer cells, the malignant phenotypes of which were evaluated by ectopic expression and knockdown methods. Collagen-activated DDR1 upregulated CXCL5 expression, resulting in augmented malignant phenotypes of breast cancer cells in vitro. The formation of NETs caused promotion in the differentiation and immune infiltration of Tregs in breast cancer. A in situ breast cancer mouse model was constructed, where NET formation and lung metastasis of breast cancer cells were observed. The differentiation of CD4+ T cells isolated from the mouse model was induced into Tregs, followed by Treg infiltration assessment. It was further confirmed in vivo that DDR1/CXCL5 induced the formation of NETs to promote immune infiltration of Tregs, driving tumor growth and metastasis. Accordingly, our results provided new mechanistic insights for an understanding of the role of collagen-mediated DDR1/CXCL5 in formation of NETs and Treg infiltration, revealing potential targets for therapeutic intervention of breast cancer.Keywords: Breast cancer; CXCL5; Collagen; DDR1; Neutrophil extracellular traps; Tregs.

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乐备实（上海优宁维生物科技股份有限公司旗下全资子公司），是国内专注于提供高质量蛋白检测以及组学分析服务的实验服务专家，自2018年成立以来，乐备实不断寻求突破，公司的服务技术平台已扩展到单细胞测序、空间多组学、流式检测、超敏电化学发光、Luminex多因子检测、抗体芯片、PCR Array、ELISA、Elispot、PLA蛋白互作、多色免疫组化、DSP空间多组学等30多个，建立起了一套涵盖基因、蛋白、细胞以及组织水平实验的完整检测体系。

 
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