Hepatocyte Growth Factor Inhibits Growth of Hepatocellular Carcinoma Cells

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 89; no. 1; pp. 373 - 377
• Main Authors: Shiota, Goshi, Rhoads, David B., Wang, Timothy C., Nakamura, Toshikazu, Schmidt, Emmett V.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01-01-1992; National Acad Sciences; National Academy of Sciences
• Subjects: Animals; Biological and medical sciences; Cancer; Carcinoma, Hepatocellular - pathology; Cell Division - drug effects; Cell growth; Cell lines; Cell physiology; Cellular biology; Cloning, Molecular; Cultured cells; DNA; Fundamental and applied biological sciences. Psychology; Gene Expression; Growth Inhibitors - genetics; Growth Inhibitors - pharmacology; Growth Substances - genetics; Growth Substances - pharmacology; Hepatocellular carcinoma; Hepatocyte Growth Factor; Hepatocytes; Humans; Liver - cytology; Liver cells; Liver Neoplasms - pathology; Liver Neoplasms, Experimental - pathology; Medical research; Mice; Mice, Nude; Mice, Transgenic; Molecular and cellular biology; Rats; Responses to growth factors, tumor promotors, other factors; RNA; RNA, Messenger - genetics; Tumor cell line; Tumor Cells, Cultured; Human; Cell proliferation; Carcinoma; Rat; Liver; Rodentia; Transgenic animal; Gene expression; Vertebrata; Mammalia; Cell line; Mouse; Polypeptide; Tumor; Inhibition; Growth factor
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.89.1.373

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.