title: Expression of ADAM33 is a novel regulatory mechanism in IL-18-secreted process in gastric cancer.
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-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.
authors.affiliation: Department of Life Science, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Kyung-Eun
authors.initials: KE
authors.lastname: Kim
authors.forename: Hyunkeun
authors.initials: H
authors.lastname: Song
authors.forename: Candace
authors.initials: C
authors.lastname: Hahm
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Yoon
authors.forename: Sunyoung
authors.initials: S
authors.lastname: Park
authors.forename: Ha-reum
authors.initials: HR
authors.lastname: Lee
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Hur
authors.forename: Taesung
authors.initials: T
authors.lastname: Kim
authors.forename: Cherl-hyun
authors.initials: CH
authors.lastname: Kim
authors.forename: Sa Ik
authors.initials: SI
authors.lastname: Bang
authors.forename: Jung-Wook
authors.initials: JW
authors.lastname: Bang
authors.forename: Hyunjeong
authors.initials: H
authors.lastname: Park
authors.forename: Dae-Ho
authors.initials: DH
authors.lastname: Cho
mesh_terms: D051722:ADAM Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D018450:Disease Progression; D004306:Dose-Response Relationship, Immunologic; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D020382:Interleukin-18 / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D008970:Molecular Weight; D011498:Protein Precursors / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D013274:Stomach Neoplasms / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000276:immunology; D042643:Vascular Endothelial Growth Factor D / Q000502:physiology
chemical_list: D020382:Interleukin-18; D011498:Protein Precursors; D012333:RNA, Messenger; D042643:Vascular Endothelial Growth Factor D; D051722:ADAM Proteins; C450441:ADAM33 protein, human