Hepatocyte growth factor inhibits growth of hepatocellular carcinoma cells.
Hepatocyte growth factor (HGF) is a potent mitogen for primary hepatocytes. Therefore, we examined HGF as a possible autocrine growth factor in hepatocellular carcinoma (HCC). We introduced an albumin-HGF expression vector into Fao HCC cells and transgenic mice. Expression of the albumin-HGF vector in Fao HCC cells inhibited their growth in vitro. In vivo, FaoHGF cells produced tumors that averaged 10% of the sizes of G418-resistant controls when transplanted into nude mice. In contrast, hepatocytes from transgenic mice expressing HGF grew more rapidly than did those from normal siblings. Further, growth of eight additional HCC cell lines was inhibited by the addition of recombinant HGF. Finally, of 35 tumor cell lines surveyed, only 6 cell lines expressed HGF mRNA, and no HCC cell line expressed HGF. Although HGF stimulates normal hepatocytes, it is a negative growth regulator for HCC cells.
Shiota
G
G
Massachusetts General Hospital Cancer Center, Charlestown 02129.
Rhoads
D B
DB
Wang
T C
TC
Nakamura
T
T
Schmidt
E V
EV
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D003001:Cloning, Molecular; D015870:Gene Expression; D006131:Growth Inhibitors / Q000235:genetics / Q000494:pharmacology; D006133:Growth Substances / Q000235:genetics / Q000494:pharmacology*; D017228:Hepatocyte Growth Factor; D006801:Humans; D008099:Liver / Q000166:cytology; D008113:Liver Neoplasms / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D014407:Tumor Cells, Cultured
D006131:Growth Inhibitors; D006133:Growth Substances; D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor