Expression of ADAM33 Is a Novel Regulatory Mechanism in IL-18-Secreted Process in Gastric Cancer

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 inv...

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Published in:	The Journal of immunology (1950) Vol. 182; no. 6; pp. 3548 - 3555
Main Authors:	Kim, Kyung-Eun, Song, Hyunkeun, Hahm, Candace, Yoon, Sun Young, Park, Sunyoung, Lee, Ha-reum, Hur, Dae Young, Kim, Taesung, Kim, Cherl-hyun, Bang, Sa Ik, Bang, Jung-Wook, Park, Hyunjeong, Cho, Dae-Ho
Format:	Journal Article
Language:	English
Published:	United States Am Assoc Immnol 15-03-2009
Subjects:	ADAM Proteins - biosynthesis ADAM Proteins - genetics ADAM Proteins - physiology Cell Line, Tumor Cell Movement - genetics Cell Movement - immunology Cell Proliferation Disease Progression Dose-Response Relationship, Immunologic Gene Expression Regulation - immunology Humans Interleukin-18 - biosynthesis Interleukin-18 - physiology Interleukin-18 - secretion Molecular Weight Protein Precursors - biosynthesis Protein Precursors - physiology Protein Precursors - secretion RNA, Messenger - biosynthesis Stomach Neoplasms - enzymology Stomach Neoplasms - immunology Stomach Neoplasms - pathology Stomach Neoplasms - secretion Up-Regulation - immunology Vascular Endothelial Growth Factor D - physiology
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Summary:	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-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 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-1767 1550-6606
DOI:	10.4049/jimmunol.0801695