IL-22 produced by cancer-associated fibroblasts promotes gastric cancer cell invasion via STAT3 and ERK signaling.
IL-22 produced by cancer-associated fibroblasts promotes gastric cancer cell invasion via STAT3 and ERK signaling.
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DOI：
10.1038/bjc.2014.336
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发表时间：
2014-08-12
影响因子：
8.8
通讯作者：
Miwa, H.
中科院分区：
文献类型：
--
作者：
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.
白细胞介素-22（IL-22）由于其在炎症过程中调节组织反应的生物学意义而最近受到重视。然而，IL-22在癌症发生中的作用仍不清楚。在此，我们研究了IL-22在胃癌组织中表达的病理生理学意义，并研究了IL-22促进胃癌细胞侵袭的机制。应用免疫组化方法检测人胃癌组织中IL-22及其受体1（IL-22 R1）的表达。采用小干扰RNA系统和特异性抑制剂检测IL-22诱导的STAT 3和ERK信号转导对胃癌细胞侵袭能力的影响。将AGS细胞与人胃癌组织中的癌相关成纤维细胞（CAFs）共培养，并通过侵袭实验进行评估。IL-22及其受体分别在胃癌组织浸润前沿的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-22 R1的表达与淋巴管浸润密切相关。IL-22通过激活STAT 3和ERK促进胃癌细胞的侵袭能力。胃癌细胞与表达IL-22的CAFs共培养后，其侵袭能力明显增强。CAFs产生的IL-22通过STAT 3和ERK信号通路促进胃癌细胞侵袭。
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. 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. 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. Interleukin-22 produced by CAFs promotes gastric cancer cell invasion via STAT3 and ERK signalling.
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影响因子：
4.7
作者：
Sekikawa, Akira;Fukui, Hirokazu;Fujimori, Takahiro
通讯作者：
Fujimori, Takahiro
影响因子：
50.3
作者：
Fukuda A;Wang SC;Morris JP 4th;Folias AE;Liou A;Kim GE;Akira S;Boucher KM;Firpo MA;Mulvihill SJ;Hebrok M
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Hebrok M
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29.4
作者：
Howlett, M;Judd, LM;Giraud, AS
通讯作者：
Giraud, AS
影响因子：
64.8
作者：
Zheng, Yan;Danilenko, Dimitry M.;Ouyang, Wenjun
通讯作者：
Ouyang, Wenjun
影响因子：
4.8
作者：
Xie, MH;Aggarwal, S;Gurney, AL
通讯作者：
Gurney, AL