Exp Mol Med.  2011 Feb;43(2):111-120. 10.3858/emm.2011.43.2.013.

Epigallocatechin-3-gallate inhibits paracrine and autocrine hepatocyte growth factor/scatter factor-induced tumor cell migration and invasion

• Kwak IH
• Shin YH
• Kim M
• Cha HY
• Nam HJ
• Lee BS
• Chaudhary
• Pai KS
• Lee JH

• KMID: 1097268
• DOI: http://doi.org/10.3858/emm.2011.43.2.013

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 microg/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.

Keyword

autocrine communication; epigallocatechin gallate; hepatocyte growth factor; neoplasm metastasis; paracrine communication; proto-oncogene proteins c-met

MeSH Terms

Animals
Autocrine Communication/*drug effects
Catechin/*analogs & derivatives/metabolism/pharmacology
Cell Line, Tumor
Cell Movement/drug effects
Female
*Hepatocyte Growth Factor
Humans
Mice
Mice, Inbred BALB C
Neoplasms, Experimental/*metabolism/pathology
Paracrine Communication/*drug effects
Phosphorylation/drug effects
Proto-Oncogene Proteins c-met/antagonists & inhibitors/metabolism
Receptors, Growth Factor/antagonists & inhibitors/metabolism
Signal Transduction