title: Epigallocatechin-3-gallate inhibits paracrine and autocrine hepatocyte growth factor/scatter factor-induced tumor cell migration and invasion.
abstract: Aberrant activation of hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, Met, is involved in the development and progression of many human cancers. In the cell-based screening assay, (-)epigallocatechin-3-gallate (EGCG) inhibited HGF/SF-Met signaling as indicated by its inhibitory activity on HGF/SF-induced cell scattering and uPA activation (IC50=15.8 microgram/ml). Further analysis revealed that EGCG at low doses specifically inhibited HGF/SF-induced tyrosine phosphorylation of Met but not epidermal growth factor (EGF)-induced phosphorylation of EGF receptor (EGFR). On the other hand, high-dose EGCG decreased both Met and EGFR proteins. We also found that EGCG did not act on the intracellular portion of Met receptor tyrosine kinase, i.e., it inhibited InlB-dependent activation of Met but not NGF-induced activation of Trk-Met hybrid receptor. This inhibition decreased HGF-induced migration and invasion by parental or HGF/SF-transfected B16F10 melanoma cells in vitro in either a paracrine or autocrine manner. Furthermore, EGCG inhibited the invasion/metastasis of HGF/SF-transfected B16F10 melanoma cells in mice. Our data suggest the possible use of EGCG in human cancers associated with dysregulated paracrine or autocrine HGF/SF-Met signaling.
authors.affiliation: Department of Biochemistry, Ajou University Medical School, Suwon, Korea.
authors.forename: In-hae
authors.initials: IH
authors.lastname: Kwak
authors.forename: Yun-Hye
authors.initials: YH
authors.lastname: Shin
authors.forename: Myeongdeok
authors.initials: M
authors.lastname: Kim
authors.forename: Hyun-Young
authors.initials: HY
authors.lastname: Cha
authors.forename: Hyun-Ja
authors.initials: HJ
authors.lastname: Nam
authors.forename: Bok-Soon
authors.initials: BS
authors.lastname: Lee
authors.forename: S C
authors.initials: SC
authors.lastname: Chaudhary
authors.forename: Ki-Soo
authors.initials: KS
authors.lastname: Pai
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects*; D002392:Catechin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D017228:Hepatocyte Growth Factor; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D019899:Paracrine Communication / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D017978:Receptors, Growth Factor; D017228:Hepatocyte Growth Factor; D002392:Catechin; C045651:epigallocatechin gallate; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met