PMID- 21351090
OWN - NLM
STAT- MEDLINE
DCOM- 20120316
LR  - 20160303
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 130
IP  - 2
DP  - 2012 Jan 15
TI  - Fibroblast growth factor-2 enhances NK sensitivity of hepatocellular carcinoma 
      cells.
PG  - 356-64
LID - 10.1002/ijc.26003 [doi]
AB  - 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-1beta 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.
CI  - Copyright (c) 2011 UICC.
FAU - Tsunematsu, Hinako
AU  - Tsunematsu H
AD  - Department of Gastroenterology and Hepatology, Osaka University Graduate School 
      of Medicine, Osaka, Japan.
FAU - Tatsumi, Tomohide
AU  - Tatsumi T
FAU - Kohga, Keisuke
AU  - Kohga K
FAU - Yamamoto, Masashi
AU  - Yamamoto M
FAU - Aketa, Hiroshi
AU  - Aketa H
FAU - Miyagi, Takuya
AU  - Miyagi T
FAU - Hosui, Atsushi
AU  - Hosui A
FAU - Hiramatsu, Naoki
AU  - Hiramatsu N
FAU - Kanto, Tatsuya
AU  - Kanto T
FAU - Hayashi, Norio
AU  - Hayashi N
FAU - Takehara, Tetsuo
AU  - Takehara T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110425
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Cytokines)
RN  - 0 (HLA Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (KLRK1 protein, human)
RN  - 0 (MHC class I-related chain A)
RN  - 0 (NK Cell Lectin-Like Receptor Subfamily C)
RN  - 0 (NK Cell Lectin-Like Receptor Subfamily K)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - EC 2.7.10.1 (FGFR2 protein, human)
RN  - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 2)
SB  - IM
MH  - Aged
MH  - Carcinoma, Hepatocellular/*immunology/pathology/virology
MH  - Cell Line, Tumor
MH  - Cytokines/biosynthesis/immunology
MH  - Female
MH  - Fibroblast Growth Factor 2/biosynthesis/blood/*immunology
MH  - HLA Antigens/biosynthesis
MH  - Hepatitis C, Chronic/immunology
MH  - Histocompatibility Antigens Class I/biosynthesis
MH  - Humans
MH  - Killer Cells, Natural/*immunology
MH  - Liver Neoplasms/*immunology/pathology/virology
MH  - Male
MH  - Middle Aged
MH  - NK Cell Lectin-Like Receptor Subfamily C/biosynthesis
MH  - NK Cell Lectin-Like Receptor Subfamily K/biosynthesis
MH  - Receptor, Fibroblast Growth Factor, Type 2/biosynthesis
EDAT- 2011/02/26 06:00
MHDA- 2012/03/17 06:00
CRDT- 2011/02/26 06:00
PHST- 2010/09/27 00:00 [received]
PHST- 2011/02/09 00:00 [accepted]
PHST- 2011/02/26 06:00 [entrez]
PHST- 2011/02/26 06:00 [pubmed]
PHST- 2012/03/17 06:00 [medline]
AID - 10.1002/ijc.26003 [doi]
PST - ppublish
SO  - Int J Cancer. 2012 Jan 15;130(2):356-64. doi: 10.1002/ijc.26003. Epub 2011 Apr 
      25.