Potentiation of invasive activity of hepatoma cells by reactive oxygen species is mediated by autocrine/paracrine loop of hepatocyte growth factor.
We have already reported that reactive oxygen species (ROS) promote rat ascites hepatoma cell invasion beneath mesentery-derived mesothelial cell monolayer. To investigate the mechanism for this, we examined the involvement of motility factors, particularly hepatocyte growth factor (HGF). Rat ascites hepatoma cell line of AH109A expressed HGF and c-Met mRNAs. Treatment with ROS augmented amounts of HGF mRNA in AH109A and HGF concentration in the medium. ROS also induced HGF gene expression in mesothelial cells. Exogenously added HGF enhanced invasive activity of AH109A cells, but exerted no effect on proliferation. AH109A cells pretreated with ROS showed an increased invasive activity, which was cancelled by simultaneous pretreatment with anti-HGF antibody. These results suggest that the invasive activity of AH109A is mediated by the autocrine and paracrine pathways of HGF, and ROS potentiate invasive activity by inducing gene expression of HGF in AH109A and mesothelial cells.
Department of Applied Biological Science, Tokyo Noko University Fuchu, Tokyo 183-8509, Japan. eiyouym@cc.tuat.ac.jp
Yutaka
Y
Miura
Yasuhiro
Y
Kozuki
Kazumi
K
Yagasaki
D000818:Animals; D019898:Autocrine Communication; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D018920:Coculture Techniques; D004357:Drug Synergism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009361:Neoplasm Invasiveness; D019899:Paracrine Communication; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D017228:Hepatocyte Growth Factor