Abstract
The roles of fibroblast growth factorโ2 (FGFโ2) in the hepatocellular carcinoma (HCC) development are still controversial. In this study, we investigated the expression of FGFโ2 in chronic hepatitis (CH) type C patients with or without HCC and the immunoregulation of FGFโ2 in NK sensitivity of HCC cells. The FGFโ2 expressions were detected in the liver tissues of patients, but not in normal liver. The serum FGFโ2 levels of the patients with CH, liver cirrhosis (LC) or HCC were significantly higher than those of healthy volunteers. The serum FGFโ2 levels of patients decreased with the progression of chronic liver disease. HCC occurrence of LC patients with high levels of serum FGFโ2 was significantly lower than that with low levels of serum FGFโ2. Proinflammatory cytokines, such as ILโ1ฮฒ and ILโ6, induced FGFโ2 expressions in HCC cells and normal hepatocytes. FGFโ2 stimulation resulted in increasing the expression of the membraneโbound major histocompatibility complex class Iโrelated chain A (MICA), an NK activating molecule, and decreasing that of human leukocyte antigen (HLA) class I, an NK inhibitory molecule, on HCC cells. This did not occur with normal hepatocytes. Adding antiโFGF receptorโ2 neutralizing antibody resulted in inhibiting the change of MICA and HLA class I expressions on FGFโ2 stimulated HCC cells. FGFโ2 stimulation on HCC cells resulted in increasing NK sensitivity against HCC cells. These findings indicate that FGFโ2 produced by HCC cells or normal hepatocytes of chronic liver disease may play critical roles in eliminating HCC cells by innate immunity.