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Fibroblast growth factor‐2 enhances NK sensitivity of hepatocellular carcinoma cells
Author(s) -
Tsunematsu Hinako,
Tatsumi Tomohide,
Kohga Keisuke,
Yamamoto Masashi,
Aketa Hiroshi,
Miyagi Takuya,
Hosui Atsushi,
Hiramatsu Naoki,
Kanto Tatsuya,
Hayashi Norio,
Takehara Tetsuo
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.26003
Subject(s) - cirrhosis , hepatocellular carcinoma , fibroblast growth factor , medicine , proinflammatory cytokine , liver disease , major histocompatibility complex , fibroblast , endocrinology , immunology , cancer research , biology , antigen , cell culture , receptor , inflammation , genetics
Abstract The roles of fibroblast growth factor‐2 (FGF‐2) in the hepatocellular carcinoma (HCC) development are still controversial. In this study, we investigated the expression of FGF‐2 in chronic hepatitis (CH) type C patients with or without HCC and the immunoregulation of FGF‐2 in NK sensitivity of HCC cells. The FGF‐2 expressions were detected in the liver tissues of patients, but not in normal liver. The serum FGF‐2 levels of the patients with CH, liver cirrhosis (LC) or HCC were significantly higher than those of healthy volunteers. The serum FGF‐2 levels of patients decreased with the progression of chronic liver disease. HCC occurrence of LC patients with high levels of serum FGF‐2 was significantly lower than that with low levels of serum FGF‐2. Proinflammatory cytokines, such as IL‐1β and IL‐6, induced FGF‐2 expressions in HCC cells and normal hepatocytes. FGF‐2 stimulation resulted in increasing the expression of the membrane‐bound major histocompatibility complex class I‐related 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 anti‐FGF receptor‐2 neutralizing antibody resulted in inhibiting the change of MICA and HLA class I expressions on FGF‐2 stimulated HCC cells. FGF‐2 stimulation on HCC cells resulted in increasing NK sensitivity against HCC cells. These findings indicate that FGF‐2 produced by HCC cells or normal hepatocytes of chronic liver disease may play critical roles in eliminating HCC cells by innate immunity.