start-ver=1.4
cd-journal=joma
no-vol=366
cd-vols=
no-issue=1
article-no=
start-page=110
end-page=116
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2008
dt-pub=20080201
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Inhibition of tumor-stromal interaction through HGF/Met signaling by valproic acid
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Hepatocyte growth factor (HGF), which is produced by surrounding stromal cells, including fibroblasts and endothelial cells, has been shown to be a significant factor responsible for cancer cell invasion mediated by tumor-stromal interactions. We found in this study that the anti-tumor agent valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, strongly inhibited tumor-stromal interaction. VPA inhibited HGF production in fibroblasts induced by epidermal growth factor (EGF), platelet-derived growth factor, basic fibroblast growth factor, phorbol 12-myristate 13-acetate (PMA) and prostaglandin E-2 without any appreciable cytotoxic effect. Other HDAC inhibitors, including butyric acid and trichostatin A (TSA), showed similar inhibitory effects on HGF production stimulated by various inducers. Up-regulations of HGF gene expression induced by PMA and EGF were also suppressed by VPA and TSA. Furthermore, VPA significantly inhibited HGF-induced invasion of HepG2 hepatocellular carcinoma cells. VPA, however, did not affect the increases in phosphorylation of MAPK and Akt in HGF-treated HepG2 cells. These results demonstrated that VPA inhibited two critical processes of tumor-stromal interaction, induction of fibroblastic HGF production and HGF-induced invasion of HepG2 cells, and suggest that those activities serve for other anti-tumor mechanisms of VPA besides causing proliferation arrest, differentiation, and/or apoptosis of tumor cells.
en-copyright=
kn-copyright=

en-aut-name=MatsumotoYohsuke
en-aut-sei=Matsumoto
en-aut-mei=Yohsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MotokiTakahiro
en-aut-sei=Motoki
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KubotaSatoshi
en-aut-sei=Kubota
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TakigawaMasaharu
en-aut-sei=Takigawa
en-aut-mei=Masaharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TsubouchiHirohito
en-aut-sei=Tsubouchi
en-aut-mei=Hirohito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=GohdaEiichi
en-aut-sei=Gohda
en-aut-mei=Eiichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

affil-num=1
en-affil=
kn-affil=Department of Immunochemistry, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=2
en-affil=
kn-affil=Department of Immunochemistry, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=3
en-affil=
kn-affil=Department of Biochemistry and Molecular Dentistry, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=4
en-affil=
kn-affil=Department of Biochemistry and Molecular Dentistry, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

affil-num=5
en-affil=
kn-affil=Digestive Disease and Life-style Related Disease, Health Research Human and Environmental Sciences, Kagoshima University, Graduate School of Medicine and Dental Sciences

affil-num=6
en-affil=
kn-affil=Department of Immunochemistry, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
en-keyword=hepatocyte growth factor
kn-keyword=hepatocyte growth factor
en-keyword=valproic acid
kn-keyword=valproic acid
en-keyword=histone deacetylase inhibitor
kn-keyword=histone deacetylase inhibitor
en-keyword=butyric acid
kn-keyword=butyric acid
en-keyword=trichostatin A
kn-keyword=trichostatin A
en-keyword=induction
kn-keyword=induction
en-keyword=tumor invasion
kn-keyword=tumor invasion
en-keyword=dermal fibroblast
kn-keyword=dermal fibroblast
END