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

• Published in: Digestive diseases and sciences Vol. 60; no. 5; pp. 1265 - 1272
• Main Authors: Yu, Xi-Xiang, Hu, Zhe, Shen, Xian, Dong, Li-Yang, Zhou, Wei-Zhong, Hu, Wen-Hao
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.05.2015; Springer; Springer Nature B.V
• Subjects: Biochemistry; Cancer; Cell Line, Tumor; Cell Movement - drug effects; Cytokines; Development and progression; Dose-Response Relationship, Drug; Enzyme Activation; Enzyme-linked immunosorbent assay; Gastroenterology; Hepatology; Humans; Interleukin-1 Receptor-Like 1 Protein; Interleukin-33; Interleukin-6 - metabolism; Interleukins - pharmacology; Matrix Metalloproteinase 3 - metabolism; Medicine; Medicine & Public Health; Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 3 - metabolism; Neoplasm Invasiveness; Oncology; Original Article; Protein Kinase Inhibitors - pharmacology; Receptors, Cell Surface - antagonists & inhibitors; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; RNA Interference; Signal Transduction - drug effects; Stomach cancer; Stomach Neoplasms - enzymology; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; Time Factors; Transfection; Transplant Surgery; ST2; ERK1/2; IL-33; Gastric cancer; Migration; Invasion
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-014-3463-1

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.