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

K. E. Kim, H. Song, T. S. Kim, D. Yoon, C. W. Kim, S. I. Bang, D. Y. Hur, H. Park, D. H. Cho

    Research output: Contribution to journalArticlepeer-review

    77 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)1468-1476
    Number of pages9
    JournalOncogene
    Volume26
    Issue number10
    DOIs
    Publication statusPublished - 2007 Mar 1

    Bibliographical note

    Funding Information:
    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.

    Keywords

    • ERK1/2
    • F-actin
    • IL-18
    • Migration
    • Tensin
    • VEGF

    ASJC Scopus subject areas

    • Molecular Biology
    • Genetics
    • Cancer Research

    Fingerprint

    Dive into the research topics of 'Interleukin-18 is a critical factor for vascular endothelial growth factor-enhanced migration in human gastric cancer cell lines'. Together they form a unique fingerprint.

    Cite this