(-)-Epigallocatechin-3-gallate (EGCG) inhibits HGF-induced invasion and metastasis in hypopharyngeal carcinoma cells.
Hepatocyte growth factor (HGF) has recently attracted a considerable amount of attention as a stromal-derived mediator in tumor-stromal interactions, particularly because of its close involvement in cancer invasion and metastasis, and (-)-epigallocatechin-3-gallate (EGCG) can modulate the cell signaling associated with angiogenesis, metastasis, and migration of cancer cells. In the present study, we have investigated the effects of HGF on invasion and metastasis of hypopharyngeal carcinoma cells and the effect of EGCG on blocking HGF-induced invasion and metastasis in these cells. We found that HGF promoted the autophosphorylation of c-Met, HGF receptor, and that HGF-induced proliferation, colony dispersion, migration and invasion of tumors. We also observed that HGF enhanced the activity of matrix metalloproteinase (MMP)-9 and urokinase-type plasminogen activator (uPA) in hypopharyngeal carcinoma cells. In addition, HGF-induced the activation of Akt and Erk pathway as a downstreaming pathway of invasion. On the other hand, EGCG at physiologically relevant concentration (1 microM) suppressed HGF-induced tumor motility and MMP-9 and uPA activities, and the suppression of Akt and Erk pathway by EGCG was one of the downstream mechanisms to facilitate EGCG-induced anti-invasion effects. These results suggest that EGCG may serve as a therapeutic agent to inhibit HGF-induced invasion in hypopharyngeal carcinoma patients.
Lim
Young Chang
YC
Department of Otorhinolaryngology, Head and Neck Surgery, Konkuk University School of Medicine, Republic of Korea.
Park
Hun Yi
HY
Hwang
Hye Sook
HS
Kang
Sung Un
SU
Pyun
Jung Hee
JH
Lee
Mi Hye
MH
Choi
Eun Chang
EC
Kim
Chul-Ho
CH
D001483:Base Sequence; D015153:Blotting, Western; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017931:DNA Primers; D004790:Enzyme Induction; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000201:enzymology / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D017228:Hepatocyte Growth Factor; D002392:Catechin; C045651:epigallocatechin gallate; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9