肿瘤相关巨噬细胞（TAM）是肿瘤微环境的主要组成部分，在肿瘤的形成和进展中发挥着关键作用；然而，TAM 诱导肿瘤进展的机制很复杂且尚不清楚。我们之前报道过，肿瘤细胞衍生的血管生成素样蛋白 2 (ANGPTL2) 在某些癌症中充当肿瘤启动子。我们检测了 221 名食管癌患者切除标本的石蜡包埋肿瘤样本中 ANGPTL2 的表达。根据上述免疫组织化学评分将患者分为四组：ANGPTL2-低/TAM-低、ANGPTL2-低/TAM-高、ANGPTL2-高/TAM-低和ANGPTL2-高/TAM-高组。食管癌细胞系的基因表达数据集来自癌细胞系百科全书公共数据库。在本研究中，我们证明TAM浸润与肿瘤细胞表现出相对较高ANGPTL2表达水平的食管癌患者预后不良相关。然而，TAM浸润并不影响ANGPTL2低表达食管癌患者的预后，这表明食管癌细胞中ANGPTL2的表达是TAM诱导的肿瘤进展所必需的。我们对公共数据集的分析表明，食管癌细胞系中 ANGPTL2 表达水平与转化生长因子 (TGF)-β（一种 TAM 激活因子）的表达水平存在潜在正相关。我们得出结论，肿瘤细胞中的 ANGPTL2 信号传导支持 TAM 诱导的肿瘤进展并导致食管癌患者预后不良。这些发现总体上为促肿瘤 ANGPTL2 功能提供了新的见解，并说明了癌细胞/TAM 串扰在癌症进展中的重要作用。© 2024。外科肿瘤学会。

Tumor-associated macrophages (TAM), a major component of the tumor microenvironment, play key roles in tumor formation and progression; however, mechanisms underlying TAM-induced tumor progression are complex and not well known. We previously reported that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) functions as a tumor promoter in some cancer contexts.We examined ANGPTL2 expression in paraffin-embedded tumor samples from resected specimens of 221 patients with esophageal cancer. Patients were subdivided into four groups based on immunohistochemistry scores described above: ANGPTL2-low/TAM-low, ANGPTL2-low/TAM-high, ANGPTL2-high/TAM-low, and ANGPTL2-high/TAM-high groups. Gene expression datasets of esophageal cancer cell lines were obtained from the cancer cell line encyclopedia public database.In this study, we demonstrate that TAM infiltration is associated with poor prognosis in patients with esophageal cancer whose tumor cells show relatively higher ANGPTL2 expression levels; however, TAM infiltration did not affect prognosis in patients with ANGPTL2-low-expressing esophageal cancer, suggesting that ANGPTL2 expression in esophageal cancer cells is required for TAM-induced tumor progression. Our analysis of public datasets indicates a potential positive correlation of ANGPTL2 expression levels with that of transforming growth factor (TGF)-β, a TAM-activating factor, in esophageal cancer cell lines.We conclude that ANGPTL2 signaling in tumor cells supports TAM-induced tumor progression and contributes to poor prognosis in patients with esophageal cancer. These findings overall provide novel insight into pro-tumor ANGPTL2 functions and illustrate the essential role of cancer cell/TAM crosstalk in cancer progression.© 2024. Society of Surgical Oncology.