Expression of ADAM33 is a novel regulatory mechanism in IL-18-secreted process in gastric cancer

Kyung Eun Kim, Hyunkeun Song, Candace Hahm, Sun Young Yoon, Sunyoung Park, Ha Reum Lee, Dae Young Hur, Taesung Kim, Cherl Hyun Kim, Sa Ik Bang, Jung Wook Bang, Hyunjeong Park, Dae Ho Cho

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31 Citations (Scopus)

Abstract

IL-18 has recently been reported to play a critical role in tumor migration, invasion, and metastasis. Because IL-18 has various biological activities after its secretion as an 18 kDa mature form, the regulation of the IL-18 secretion process is an important step in tumor progression. This study investigated the implication of IL-18 in vascular endothelial growth factor (VEGF)-D-regulated migration, along with the role of the IL-18 secretion process. VEGF-D enhanced cell migration, which was then blocked by inhibiting IL-18. VEGF-D increased IL-18 expression and secretion, suggesting that IL-18 is a critical mediator for VEGF-Denhanced migration. VEGF-D induced a disintegrin and metalloprotease 33 (ADAM33) expression, which has a metalloproteinase domain. VEGF-D-enhanced IL-18 secretion and cell migration were inhibited by ADAM33 knock-down. Moreover, cell proliferation was considerably reduced in ADAM33 small interfering RNA transfectants. In conclusion, ADAM33 has a key role in gastric cancer pathogenesis by up-regulating IL-18 secretion process, resulting in increased cell migration and proliferation.

Original languageEnglish
Pages (from-to)3548-3555
Number of pages8
JournalJournal of Immunology
Volume182
Issue number6
DOIs
Publication statusPublished - 2009 Mar 15

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Kim, K. E., Song, H., Hahm, C., Yoon, S. Y., Park, S., Lee, H. R., Hur, D. Y., Kim, T., Kim, C. H., Bang, S. I., Bang, J. W., Park, H., & Cho, D. H. (2009). Expression of ADAM33 is a novel regulatory mechanism in IL-18-secreted process in gastric cancer. Journal of Immunology, 182(6), 3548-3555. https://doi.org/10.4049/jimmunol.0801695