IFI16 Induced by Direct Interaction between Esophageal Squamous Cell Carcinomas and Macrophages Promotes Tumor Progression via Secretion of IL-1α

被引:4
作者
Azumi, Yuki [1 ,2 ]
Koma, Yu-ichiro [1 ]
Tsukamoto, Shuichi [1 ]
Kitamura, Yu [2 ]
Ishihara, Nobuaki [1 ,3 ]
Yamanaka, Keitaro [1 ,4 ]
Nakanishi, Takashi [1 ,2 ]
Miyako, Shoji [1 ,2 ]
Urakami, Satoshi [1 ,5 ]
Tanigawa, Kohei [2 ]
Kodama, Takayuki [1 ]
Nishio, Mari [1 ]
Shigeoka, Manabu [1 ]
Kakeji, Yoshihiro [2 ]
Yokozaki, Hiroshi [1 ]
机构
[1] Kobe Univ, Grad Sch Med, Dept Pathol, Div Pathol, Kobe 6500017, Japan
[2] Kobe Univ, Dept Surg, Div Gastrointestinal Surg, Grad Sch Med, Kobe 6500017, Japan
[3] Kobe Univ, Grad Sch Med, Dept Surg, Div Hepatobiliary Pancreat Surg, Kobe 6500017, Japan
[4] Kobe Univ, Dept Surg Related, Div Obstet & Gynecol, Grad Sch Med, Kobe 6500017, Japan
[5] Kobe Univ, Grad Sch Med, Dept Internal Med, Div Gastroenterol, Kobe 6500017, Japan
关键词
esophageal squamous cell carcinoma; tumor-associated macrophage; direct co-culture; IFI16; IL-1; alpha; CANCER; ANTIBODIES; ANTI-IFI16; DISEASE; FAMILY; SENSOR;
D O I
10.3390/cells12222603
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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-1 alpha (IL-1 alpha) from ESCC cells. Additionally, recombinant IL-1 alpha enhanced malignant phenotypes of ESCC cells through the Erk and NF-kappa B 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-1 alpha and imply the potential of IFI16 as a novel prognostic factor for ESCC.
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页数:18
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