Interleukin-18 is a critical factor for vascular endothelial growth factor-enhanced migration in human gastric cancer cell lines.
Cell migration and angiogenesis are key steps in tumor metastasis. However, the mechanism of migration regulated by vascular endothelial growth factor (VEGF), a potent regulator of angiogenesis, is not completely understood. This study examined the relationship between VEGF and migration, along with the mechanism involved in the VEGF-regulated migration of human gastric cancer cells. The level of cell migration was increased by recombinant human (rh)VEGF-165 in the VEGF receptor-2-expressing SNU-601 cells. Interleukin (IL)-18 is associated with the malignant progression of tumors. Accordingly, this study examined the effect of IL-18 on the migration of cancer cells in order to identify the factors involved in VEGF-enhanced migration. Inhibiting IL-18 markedly reduced the level of VEGF-enhanced migration, and IL-18 increased cell migration directly through filamentous-actin polymerization and tensin downregulation. It was confirmed that rhVEGF-165 increased IL-18 production significantly. An antioxidant and an extracellular signal-regulated kinase (ERK)1/2-specific inhibitor blocked rhVEGF-165-enhanced IL-18 production. Accordingly, rhVEGF-165 increased the generation of region of interest (ROI) and activated the ERK1/2 pathway. These results suggest that rhVEGF-165 enhances IL-18 production via the generation of ROI and ERK1/2 phosphorylation, which results in the increased migration of gastric cancer cells.
Kim
K-E
KE
Department of Life Science, Sookmyung Women's University, Yongsan-ku, Seoul, Korea.
Song
H
H
Kim
T S
TS
Yoon
D
D
Kim
C-w
CW
Bang
S I
SI
Hur
D Y
DY
Park
H
H
Cho
D-H
DH
D000199:Actins / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D006801:Humans; D020382:Interleukin-18 / Q000502:physiology*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*; D000070876:Tensins; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
D000199:Actins; D020382:Interleukin-18; D008840:Microfilament Proteins; D011994:Recombinant Proteins; D000070876:Tensins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D020930:MAP Kinase Kinase Kinases