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- Title
Interleukin-18 is a critical factor for vascular endothelial growth factor-enhanced migration in human gastric cancer cell lines.
- Authors
Kim, K.-E.; Song, H.; Kim, T. S.; Yoon, D.; Kim, C.-W.; Bang, S. I.; Hur, D. Y.; Park, H.; Cho, D.-H.
- Abstract
Cell migration and angiogenesis are key steps in tumor metastasis. However, the mechanism of migration regulated by vascular endothelial growth factor (VEGF), a potent regulator of angiogenesis, is not completely understood. This study examined the relationship between VEGF and migration, along with the mechanism involved in the VEGF-regulated migration of human gastric cancer cells. The level of cell migration was increased by recombinant human (rh)VEGF-165 in the VEGF receptor-2-expressing SNU-601 cells. Interleukin (IL)-18 is associated with the malignant progression of tumors. Accordingly, this study examined the effect of IL-18 on the migration of cancer cells in order to identify the factors involved in VEGF-enhanced migration. Inhibiting IL-18 markedly reduced the level of VEGF-enhanced migration, and IL-18 increased cell migration directly through filamentous-actin polymerization and tensin downregulation. It was confirmed that rhVEGF-165 increased IL-18 production significantly. An antioxidant and an extracellular signal-regulated kinase (ERK)1/2-specific inhibitor blocked rhVEGF-165-enhanced IL-18 production. Accordingly, rhVEGF-165 increased the generation of region of interest (ROI) and activated the ERK1/2 pathway. These results suggest that rhVEGF-165 enhances IL-18 production via the generation of ROI and ERK1/2 phosphorylation, which results in the increased migration of gastric cancer cells.Oncogene (2007) 26, 1468–1476. doi:10.1038/sj.onc.1209926; published online 25 September 2006
- Subjects
CANCER; GASTRIC diseases; METASTASIS; CONTINUOUS cell lines; CELL migration; INTERLEUKINS; VASCULAR endothelial growth factors
- Publication
Oncogene, 2007, Vol 26, Issue 10, p1468
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1209926