炎性细胞外基质的改变塑造了肿瘤微环境，并促进了癌症发生的各个阶段。本研究旨在确定细胞纤维连接蛋白对乳腺癌肿瘤相关巨噬细胞（TAMs）炎性特征的影响。细胞纤维连接蛋白（FN）含有可变剪接的额外区域A（FN-EDA），是三阴性乳腺癌（TNBC）细胞产生的基质成分。FN-EDA水平高与乳腺癌患者的生存率低相关。促炎性细胞因子IL-1β增强了包括FN-EDA在内的细胞纤维连接蛋白的表达。在富含FN-EDA的肿瘤区域中经常观察到TAMs。来源于TNBC细胞的培养基诱导CD206 + CD163 +巨噬细胞分化，并刺激STAT3途径，外部。在巨噬细胞中，STAT3途径增强了FN-EDA诱导的IL-1β分泌和NF-κB信号。总之，我们的数据表明，在TAM中，FN-EDA和IL-1β通过NF-κB和STAT3信号的自我协同增强机制促进了TNBC的炎性环境。©2023该作者。

Inflammatory alterations of the extracellular matrix shape the tumor microenvironment and promote all stages of carcinogenesis. This study aims to determine the impact of cellular fibronectin on inflammatory facets of tumor-associated macrophages (TAMs) in breast cancer. Cellular fibronectin (FN) harboring the alternatively spliced extra domain A (FN-EDA) was determined to be a matrix component produced by the triple-negative breast cancer (TNBC) cells. High levels of FN-EDA correlated with poor survival in breast cancer patients. The proinflammatory cytokine IL-1β enhanced the expression of cellular fibronectin including FN-EDA. TAMs were frequently observed in the tumor areas rich in FN-EDA. Conditioned media from TNBC cells induced the differentiation of CD206+CD163+ macrophages and stimulated the STAT3 pathway, ex vivo. In the macrophages, the STAT3 pathway enhanced FN-EDA-induced IL-1β secretion and NF-κB signaling. In conclusion, our data indicate a self-reinforcing mechanism sustained by FN-EDA and IL-1β through NF-κB and STAT3 signaling in TAMs which fosters an inflammatory environment in TNBC.© 2023. The Author(s).