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白细胞介素-33通过ST2-ERK1/2途径促进胃癌细胞的侵袭和迁移。

IL-33 Promotes Gastric Cancer Cell Invasion and Migration Via ST2-ERK1/2 Pathway.

作者信息

Yu Xi-Xiang, Hu Zhe, Shen Xian, Dong Li-Yang, Zhou Wei-Zhong, Hu Wen-Hao

机构信息

Department of Interventional Radiology, The Third Affiliated Hospital of Wenzhou Medical University, Ruian, Zhejiang, China,

出版信息

Dig Dis Sci. 2015 May;60(5):1265-72. doi: 10.1007/s10620-014-3463-1. Epub 2015 Feb 6.

DOI:10.1007/s10620-014-3463-1
PMID:25655003
Abstract

BACKGROUND

As a pro-inflammatory cytokine, IL-33 has been demonstrated to play an important role in tumor progression. It is reported that IL-33 is highly expressed in the serum and tumor tissues of patients with gastric cancer. However, the function of IL-33 in gastric cancer remains elusive. We here tried to elucidate the effects of IL-33 on gastric cancer cell invasion and migration.

METHODS

Invasion assay and migration assay were performed to assess the effects of IL-33 on gastric cancer cell invasion and migration. ST2 receptor was silenced by siRNA, and ERK1/2 pathway was inhibited by U0126. Protein levels of MMP-3 and IL-6 in cell supernatant were measured by ELISA.

RESULTS

IL-33 promoted the invasion and migration of gastric cancer cells, in a dose-dependent manner. Knockdown of the IL-33 receptor ST2 attenuated the IL-33-mediated invasion and migration. Furthermore, via ST2 receptor, IL-33 induced the activation of ERK1/2 and increased the secretion of MMP-3 and IL-6. In addition, blockage of ERK1/2 pathway resulted in inhibition of invasion and migration induced by IL-33, and downregulation of MMP-3 and IL-6 production.

CONCLUSIONS

IL-33 promotes gastric cancer cell invasion and migration by stimulating the secretion of MMP-3 and IL-6 via ST2-ERK1/2 pathway. Thus, IL-33 may be a useful marker for the diagnosis and treatment of gastric cancer.

摘要

背景

作为一种促炎细胞因子，白细胞介素-33（IL-33）已被证明在肿瘤进展中起重要作用。据报道，IL-33在胃癌患者的血清和肿瘤组织中高表达。然而，IL-33在胃癌中的功能仍不清楚。我们在此试图阐明IL-33对胃癌细胞侵袭和迁移的影响。

方法

进行侵袭试验和迁移试验以评估IL-33对胃癌细胞侵袭和迁移的影响。通过小干扰RNA（siRNA）使ST2受体沉默，并用U0126抑制细胞外信号调节激酶1/2（ERK1/2）通路。采用酶联免疫吸附测定法（ELISA）检测细胞上清液中基质金属蛋白酶-3（MMP-3）和白细胞介素-6（IL-6）的蛋白水平。

结果

IL-33以剂量依赖的方式促进胃癌细胞的侵袭和迁移。敲低IL-33受体ST2可减弱IL-33介导的侵袭和迁移。此外，IL-33通过ST2受体诱导ERK1/2激活，并增加MMP-3和IL-6的分泌。此外，阻断ERK1/2通路可导致IL-33诱导的侵袭和迁移受到抑制，以及MMP-3和IL-6产生下调。

结论

IL-33通过ST2-ERK1/2通路刺激MMP-3和IL-6的分泌，从而促进胃癌细胞的侵袭和迁移。因此，IL-33可能是胃癌诊断和治疗的一个有用标志物。

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Significance of interleukin-33 and its related cytokines in patients with breast cancers.白细胞介素-33 及其相关细胞因子在乳腺癌患者中的意义。
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Serum soluble ST2 is associated with ER-positive breast cancer.血清可溶性 ST2 与 ER 阳性乳腺癌相关。
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Mesenchymal stem cell origin contributes to the antitumor effect of oncolytic virus carriers.间充质干细胞来源有助于溶瘤病毒载体的抗肿瘤作用。
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The Importance of Th2 Immune Responses in Mediating the Progression of Gastritis-Associated Metaplasia to Gastric Cancer.Th2免疫反应在介导胃炎相关化生进展为胃癌过程中的重要性。
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Interleukin-33/ST2 axis promotes breast cancer growth and metastases by facilitating intratumoral accumulation of immunosuppressive and innate lymphoid cells.白细胞介素-33/ST2 轴通过促进肿瘤内免疫抑制性和固有淋巴细胞的积累促进乳腺癌的生长和转移。
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