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 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.
Kim
Kyung-Eun
KE
Department of Life Science, Sookmyung Women's University, Seoul, Republic of Korea.
Song
Hyunkeun
H
Hahm
Candace
C
Yoon
Sun Young
SY
Park
Sunyoung
S
Lee
Ha-reum
HR
Hur
Dae Young
DY
Kim
Taesung
T
Kim
Cherl-hyun
CH
Bang
Sa Ik
SI
Bang
Jung-Wook
JW
Park
Hyunjeong
H
Cho
Dae-Ho
DH
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
D020382:Interleukin-18; D011498:Protein Precursors; D012333:RNA, Messenger; D042643:Vascular Endothelial Growth Factor D; D051722:ADAM Proteins; C450441:ADAM33 protein, human