ADAM33 regulates IL-18-secreted process in gastric cancer cells
- Authors
- Kim, Kyung-Eun; Cho, Dae-Ho
- Issue Date
- Apr-2009
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Citation
- JOURNAL OF IMMUNOLOGY, v.182, no.1
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Volume
- 182
- Number
- 1
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/13778
- ISSN
- 0022-1767
1550-6606
- Abstract
- Interleukin (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 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 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-D-enhanced 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 siRNA 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.
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