Expression of hepatoma-derived growth factor in hepatocarcinogenesis.
OBJECTIVE
The present study investigated the expression of hepatoma-derived growth factor (HDGF) in human hepatocellular carcinoma (HCC) and in the liver during hepatocarcinogenesis in two rodent models.


METHODS
Expression of HDGF was analyzed using northern blotting and immunohistochemistry in the human and rodent models.


RESULTS
Hepatoma-derived growth factor was more highly expressed in HCC than in the adjacent liver in humans with hepatitis, as shown by northern blotting. Using immunohistochemistry with the specific anti-HDGF antibody, HDGF was more strongly and frequently expressed in the nucleus and cytoplasm of HCC cells than in the adjacent normal hepatocytes. Hepatoma-derived growth factor was also more strongly expressed in the tumors than in the adjacent fatty liver of fatty liver Shionogi (FLS) mice, than in the cirrhotic liver of choline-deficient amino acid feeding rats, as shown by northern blotting and immunohistochemistry. In the liver of FLS mice, HDGF expression increased gradually from the age of 24 weeks through to 52 weeks after birth, showing that HDGF expression was already increased at an early stage before tumor development. In the non-tumorous liver with fatty change, the foci expressing HDGF appeared at 24 weeks of age, which were the activated macrophage clusters with enhanced DNA synthesis and fat droplets. It is suggested that HDGF was secreted or released from these foci and stimulated hepatocyte proliferation in a paracrine manner in FLS mice, and stimulated the proliferation of hepatic tumor cells in an autocrine manner.


CONCLUSIONS
The present findings suggest that HDGF plays an important role in the development or progression of HCC in humans and rodents.
Yoshida
Kenya
K
Department of Molecular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Nakamura
Hideji
H
Okuda
Yorihide
Y
Enomoto
Hirayuki
H
Kishima
Yoshihiko
Y
Uyama
Hirokazu
H
Ito
Hiroaki
H
Hirasawa
Tsutomu
T
Inagaki
Shuichiro
S
Kawase
Ichiro
I
D000818:Animals; D000911:Antibodies, Monoclonal; D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000032:analysis; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D011916:Rats, Inbred F344
D000911:Antibodies, Monoclonal; D004273:DNA, Neoplasm; D036341:Intercellular Signaling Peptides and Proteins; C051610:hepatoma-derived growth factor