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Interleukin-18 is a critical factor for vascular endothelial growth factor-enhanced migration in human gastric cancer cell lines

Oncogene volume 26, pages 1468–1476 (2007)Cite this article

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.

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Acknowledgements

This work was supported by the Korea Science & Engineering Foundation (KOSEF) through the Tumor Immunity Medical Research Center (TIMRC) at Seoul National University College of Medicine and through the Research Center for Women's Disease (RCWD; SRC program (R11-2005-017-02003-0)) at Sookmyung Women's University.

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Author notes

  1. K-E Kim and H Song: These authors contributed equally to this task.

Authors and Affiliations

  1. Department of Life Science, Sookmyung Women's University, Yongsan-ku, Seoul, Korea

    K-E Kim & D-H Cho

  2. Department of Anatomy, Inje University College of Medicine, Pusan, Korea

    H Song & D Y Hur

  3. School of Life Science and Technology, Korea University, Seoul, Korea

    T S Kim

  4. Division of Bioscience and Biotechnology, Konkuk University Graduate School, Seoul, Korea

    D Yoon

  5. Department of Pathology and Tumor Immunity Medical Research Center, Seoul National University, College of Medicine, Seoul, Korea

    C-w Kim

  6. Department of Plastic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

    S I Bang

  7. Department of Dermatology, St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea

    H Park

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  1. K-E Kim
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Correspondence to H Park or D-H Cho.

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Kim, KE., Song, H., Kim, T. et al. Interleukin-18 is a critical factor for vascular endothelial growth factor-enhanced migration in human gastric cancer cell lines. Oncogene 26, 1468–1476 (2007). https://doi.org/10.1038/sj.onc.1209926

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