The microarray analysis has revealed that NGF is specifically elevated in mouse hepatocellular carcinomas. The present study aimed to elucidate expression of NGF and its receptors (TrkA and p75NTR) during hepatic carcinogenesis, regeneration, development and primary hepatocyte culture in mice. Although NGF was negative or very weakly expressed in adult and developing livers, it was markedly elevated in neoplastic hepatocytic lesions from early stages of carcinogenesis. Appreciable levels were also detected in regenerating livers and hepatocyte cultures. The conditioned medium of hepatocellular carcinoma cells caused PC12 neurite outgrowth, but this was reduced with pretreatment of the conditioned medium with the anti-NGF antibody or NGF antisense expression in hepatocellular carcinoma cells. Although neither TrkA nor p75NTR was detectable in either hepatocellular carcinoma or normal hepatic cells, TrkA was demonstrated in the walls of tumor associated arteries that contain abundant nerve fibers. This study demonstrated that NGF is expressed by hepatocytes during carcinogeneis, regeneration and primary culture, but may have cells other than hepatocytes as the target. TrkA expression and abundance of nerve fibers in the walls of tumor-associated arteries suggest some possible role for NGF in angiogenesis.
注記
W B Saunders, Kan, Kishibe; Yoshihisa, Yamada; Katsuhiro, Ogawa, GASTROENTEROLOGY, 122(7), 2002, 1978-1986
