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Abstract：
Tumor-associated macrophages (TAMs), one of the major components of the tumor microenvironment, contribute to the progression of esophageal squamous cell carcinoma (ESCC). We previously established a direct co-culture system of human ESCC cells and macrophages and reported the promotion of malignant phenotypes, such as survival, growth, and migration, in ESCC cells. These findings suggested that direct interactions between cancer cells and macrophages contribute to the malignancy of ESCC, but its underlying mechanisms remain unclear. In this study, we compared the expression levels of the interferon-induced genes between mono- and co-cultured ESCC cells using a cDNA microarray and found that interferon-inducible protein 16 (IFI16) was most significantly upregulated in co-cultured ESCC cells. IFI16 knockdown suppressed malignant phenotypes and also decreased the secretion of interleukin-1α (IL-1α) from ESCC cells. Additionally, recombinant IL-1α enhanced malignant phenotypes of ESCC cells through the Erk and NF-κB signaling. Immunohistochemistry revealed that high IFI16 expression in human ESCC tissues tended to be associated with disease-free survival and was significantly associated with tumor depth, lymph node metastasis, and macrophage infiltration. The results of this study reveal that IFI16 is involved in ESCC progression via IL-1α and imply the potential of IFI16 as a novel prognostic factor for ESCC.
摘要：
肿瘤相关巨噬细胞（TAMs），肿瘤微环境的主要组成部分之一，有助于食管鳞状细胞癌（ESCC）的进展。我们先前建立了人类ESCC细胞和巨噬细胞的直接共培养系统，并报道了恶性表型的促进，比如生存，增长,和移民,在ESCC细胞中。这些结果表明，癌细胞和巨噬细胞之间的直接相互作用有助于ESCC的恶性，但其潜在机制仍不清楚。在这项研究中,我们使用cDNA微阵列比较了单培养和共培养的ESCC细胞之间干扰素诱导基因的表达水平,发现干扰素诱导蛋白16(IFI16)在共培养的ESCC细胞中表达上调最为显著.IFI16敲低抑制了恶性表型，也减少了ESCC细胞中白细胞介素-1α（IL-1α）的分泌。此外,重组IL-1α通过Erk和NF-κB信号增强ESCC细胞的恶性表型。免疫组织化学显示，IFI16在人ESCC组织中的高表达倾向于与无病生存率相关，并与肿瘤深度显着相关。淋巴结转移,和巨噬细胞浸润。这项研究的结果表明，IFI16通过IL-1α参与ESCC的进展，并暗示IFI16可能成为ESCC的新预后因素。
