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癌症相关成纤维细胞产生的白细胞介素-22通过信号转导和转录激活因子3（STAT3）及细胞外信号调节激酶（ERK）信号通路促进胃癌细胞侵袭。

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

作者信息

Fukui H, Zhang X, Sun C, Hara K, Kikuchi S, Yamasaki T, Kondo T, Tomita T, Oshima T, Watari J, Imura J, Fujimori T, Sasako M, Miwa H

机构信息

Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.

1] Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Japan [2] Department of Geriatric Digestive Internal Medicine, Sichuan Academy of Medical Science & Sichuan People's Hospital, Chengdu 610072, China.

出版信息

Br J Cancer. 2014 Aug 12;111(4):763-71. doi: 10.1038/bjc.2014.336. Epub 2014 Jun 17.

DOI:10.1038/bjc.2014.336
PMID:24937671
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4134496/
Abstract

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 α-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.

摘要

背景

白细胞介素-22（IL-22）因其在炎症过程中调节组织反应的生物学意义而受到关注。然而，IL-22在致癌作用中的角色仍不明确。在此，我们研究了IL-22在胃癌组织中表达的病理生理意义，并探讨了IL-22促进胃癌细胞侵袭的机制。

方法

采用免疫组织化学方法分析人胃癌标本中IL-22和IL-22受体1（IL-22R1）的表达。利用小干扰RNA系统和特异性抑制剂检测IL-22诱导的信号转导及转录激活因子3（STAT3）和细胞外调节蛋白激酶（ERK）信号对胃癌细胞侵袭能力的影响。将AGS细胞与人胃癌组织来源的癌相关成纤维细胞（CAFs）共培养，并通过侵袭实验进行评估。

结果

IL-22及其受体分别在胃癌组织侵袭前沿的α平滑肌肌动蛋白阳性基质细胞和肿瘤细胞中表达。IL-22和IL-22R1的表达与淋巴侵袭显著相关。IL-22处理通过激活STAT3和ERK促进胃癌细胞的侵袭能力。与表达IL-22的CAFs共培养可显著增强胃癌细胞的侵袭能力。

结论

CAFs产生的IL-22通过STAT3和ERK信号通路促进胃癌细胞侵袭。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/110c/4134496/cb75cd54906d/bjc2014336f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/110c/4134496/5334340a49f8/bjc2014336f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/110c/4134496/0b759a45420b/bjc2014336f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/110c/4134496/29e4f6ecd1fa/bjc2014336f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/110c/4134496/293d8a5e7a3c/bjc2014336f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/110c/4134496/cb75cd54906d/bjc2014336f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/110c/4134496/5334340a49f8/bjc2014336f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/110c/4134496/0b759a45420b/bjc2014336f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/110c/4134496/29e4f6ecd1fa/bjc2014336f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/110c/4134496/293d8a5e7a3c/bjc2014336f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/110c/4134496/cb75cd54906d/bjc2014336f5.jpg

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