Tumor‐associated macrophages (TAMs) play a pivotal role in facilitating tumor growth and metastasis. This tumor‐promoting propensity of TAMs sets in as a result of their complex cross‐talk with tumor cells mediated primarily by tumor cell‐secreted proteins in the tumor microenvironment. To explore such interactions, we employed an immunoscreening approach involving the immunization of Balb‐c mice with model human lung carcinoma cell line, A549. From serological examination combined with mass spectrometric analysis, EDA‐containing fibronectin (EDA_FN) was identified as a conspicuous immunogenic protein in A549 cell secretome. We showed that A549 secreted EDA_FN engages TLR‐4 on THP‐1 monocytes to drive the proinflammatory response via NF‐κB signaling cascade. Conversely, A549 derived EDA_FN potentiates their metastatic capacity by inducing epithelial–mesenchymal transition through its autocrine activity. In conclusion, the study proposes a possible mechanism of cellular cross‐talk between lung cancer cells and associated monocytes mediated by lung cancer‐derived EDA_FN and resulting in the establishment of proinflammatory and metastatic tumor microenvironment.

中文翻译：

---

肺癌细胞衍生的含有 EDA 的纤连蛋白诱导单核细胞的炎症反应并促进转移性肿瘤微环境

肿瘤相关巨噬细胞（TAM）在促进肿瘤生长和转移方面发挥着关键作用。TAM 的这种促肿瘤倾向是由于它们与肿瘤细胞主要由肿瘤微环境中的肿瘤细胞分泌蛋白介导的复杂串扰而产生的。为了探索这种相互作用，我们采用了一种免疫筛选方法，涉及用模型人肺癌细胞系 A549 对 Balb-c 小鼠进行免疫。从血清学检查结合质谱分析，含有 EDA 的纤连蛋白 (EDA _FN ) 被鉴定为 A549 细胞分泌组中显着的免疫原性蛋白。我们发现 A549 分泌的 EDA _FN与 THP-1 单核细胞上的 TLR-4 结合，通过 NF-κB 信号级联来驱动促炎反应。相反，A549衍生的EDA_FN通过其自分泌活性诱导上皮间质转化，从而增强其转移能力。总之，该研究提出了肺癌细胞与相关单核细胞之间由肺癌衍生的 EDA _FN介导的细胞串扰的可能机制，并导致促炎和转移性肿瘤微环境的建立。