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

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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.

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Authors and Affiliations

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

    Xi-Xiang Yu

  2. Department of Interventional Radiology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China

    Zhe Hu

  3. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

    Xian Shen

  4. Department of Interventional Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

    Li-Yang Dong & Wei-Zhong Zhou

  5. Department of Interventional Radiology, The First Affiliated Hospital of Wenzhou Medical University, 2 Fu Xue Road, Wenzhou, 325000, Zhejiang, China

    Wen-Hao Hu

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  1. Xi-Xiang Yu
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  2. Zhe Hu
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  3. Xian Shen
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  4. Li-Yang Dong
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  5. Wei-Zhong Zhou
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  6. Wen-Hao Hu
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Correspondence to Wen-Hao Hu.

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Yu, XX., Hu, Z., Shen, X. et al. IL-33 Promotes Gastric Cancer Cell Invasion and Migration Via ST2–ERK1/2 Pathway. Dig Dis Sci 60, 1265–1272 (2015). https://doi.org/10.1007/s10620-014-3463-1

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  • DOI: https://doi.org/10.1007/s10620-014-3463-1

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