RRC ID 78167
著者 Azumi Y, Koma YI, Tsukamoto S, Kitamura Y, Ishihara N, Yamanaka K, Nakanishi T, Miyako S, Urakami S, Tanigawa K, Kodama T, Nishio M, Shigeoka M, Kakeji Y, Yokozaki H.
タイトル IFI16 Induced by Direct Interaction between Esophageal Squamous Cell Carcinomas and Macrophages Promotes Tumor Progression via Secretion of IL-1α.
ジャーナル Cells
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.
巻・号 12(22)
公開日 2023-11-10
DOI 10.3390/cells12222603
PII cells12222603
PMID 37998338
PMC PMC10670642
MeSH Carcinoma, Squamous Cell* / pathology Cell Line, Tumor Esophageal Neoplasms* / pathology Esophageal Squamous Cell Carcinoma* / genetics Esophageal Squamous Cell Carcinoma* / pathology Humans Interferons / metabolism Interleukin-1alpha / metabolism Macrophages / metabolism Neoplastic Processes Nuclear Proteins / metabolism Phosphoproteins / metabolism Tumor Microenvironment
リソース情報
ヒト・動物細胞 TE-9(RCB1988) TE-10(RCB2099) TE-11(RCB2100)