Published in:
01-05-2015 | Original Article
IL-33 Promotes Gastric Cancer Cell Invasion and Migration Via ST2–ERK1/2 Pathway
Published in: Digestive Diseases and Sciences | Issue 5/2015
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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.