IL-22 produced by cancer-associated fibroblasts promotes gastric cancer cell invasion via STAT3 and ERK signaling

被引：88
作者：
Fukui, H. [1 ]
Zhang, X. [1 ,2 ,3 ]
Sun, C. [1 ,4 ]
Hara, K. [1 ]
Kikuchi, S. [5 ]
Yamasaki, T. [1 ]
Kondo, T. [1 ]
Tomita, T. [1 ]
Oshima, T. [1 ]
Watari, J. [1 ]
Imura, J. [6 ]
Fujimori, T. [6 ]
Sasako, M. [5 ]
Miwa, H. [1 ]
机构：
[1] Hyogo Coll Med, Dept Internal Med, Div Gastroenterol, Nishinomiya, Hyogo 6638501, Japan
[2] Sichuan Acad Med Sci, Dept Geriatr Digest Internal Med, Chengdu 610072, Peoples R China
[3] Sichuan Peoples Hosp, Chengdu 610072, Peoples R China
[4] Tianjin Med Univ, Gen Hosp, Dept Digest Dis, Tianjin 300052, Peoples R China
[5] Hyogo Coll Med, Dept Surg, Nishinomiya, Hyogo 6638501, Japan
[6] Dokkyo Univ, Sch Med, Dept Surg & Mol Pathol, Mibu, Tochigi 3210293, Japan
来源：
BRITISH JOURNAL OF CANCER | 2014年 / 111卷 / 04期
关键词：
IL-22; invasion; gastric cancer; STAT3; ERK; cancer-associated fibroblast; INTERLEUKIN (IL)-22; POOR-PROGNOSIS; EXPRESSION; CYTOKINE; INITIATION; CARCINOMA; IL-10;
D O I：
10.1038/bjc.2014.336
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Background: Interleukin-22 (IL-22) has been recently highlighted owing to its biological significance in the modulation of tissue responses during inflammation. However, the role of IL-22 in carcinogenesis has remained unclear. Here, we investigated the pathophysiological significance of IL-22 expression in gastric cancer tissues and examined the mechanism by which IL-22 promotes gastric cancer cell invasion. Methods: Human gastric cancer specimens were analysed by immunohistochemistry for expression of IL-22 and IL-22 receptor 1 (IL-22R1). The effects of IL-22-induced STAT3 and ERK signalling on invasive ability of gastric cancer cells were examined using a small-interfering RNA system and specific inhibitors. AGS cells were co-cultured with cancer-associated fibroblasts (CAFs) from human gastric cancer tissues and assessed by invasion assay. Results: Interleukin-22 and its receptor were expressed in alpha-smooth muscle actin-positive stromal cells and tumour cells at the invasive front of gastric cancer tissues, respectively. The expression of IL-22 and IL-22R1 was significantly related to lymphatic invasion. Interleukin-22 treatment promoted the invasive ability of gastric cancer cells through STAT3 and ERK activation. The invasive ability of gastric cancer cells was significantly enhanced by co-culture with IL-22-expressing CAFs. Conclusions: Interleukin-22 produced by CAFs promotes gastric cancer cell invasion via STAT3 and ERK signalling.
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收藏
页码：763 / 771
页数：9
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