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Int J Clin Exp Pathol 2010;3(6):634-639

Case Report
Matrix metalloproteinase-1 expression in splenic angiosarcoma metastasizing to the
serous membrane

Tamotsu Takeuchi, Shinji Iwasaki, Junichi Miyazaki, Yasuko Nozaki, Masaya Takahashi, Masafumi Ono, Toshiji Saibara, Mutsuo Furihata

Department of Pathology, Department of Gastroenterology and Hepatology, Kochi Medical School, Nankoku, Japan 783-8505, and Department
of Clinical Pathology, Kochi Prefectural Hata Kenmin Hospital, Kochi, Japan 788-0785

Received June 9, 2010, accepted June 28, 2010, available online July 4, 2010

Abstract: Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation which starts with simple hepatic steatosis
and may progress toward inflammation (nonalcoholic steatohepatitis [NASH]). Fatty acid synthase (FASN) catalyzes the last step in fatty acid
biosynthesis, and thus, it is believed to be a major determinant of the maximal hepatic capacity to generate fatty acids by de novo lipogenesis.
The aim of this study was to analyze the correlation between hepatic steatosis and inflammation with FASN expression. In vitro incubation of
primary human hepatocytes with fatty acids dose-dependently induced cellular fatty acidaccumulation and FASN expression, while stimulation
with TNF did not affect FASN levels. Further, hepatic FASN expression was significantly increased in vivo in a murine model of hepatic steatosis
without significant inflammation but not in a murine NASH model as compared to control mice. Also, FASN expression was not increased
in mice subjected to bile duct ligation, an experimental model characterized by severe hepatocellular damage and inflammation. Furthermore,
FASN expression was analyzed in 102 human control or NAFLD livers applying tissue micro array technology and immunohistochemistry, and
correlated significantly with the degree of hepatic steatosis, but not with inflammation or ballooning of hepatocytes. Quantification of FASN
mRNA expression in human liver samples confirmed significantly higher FASN levels in hepatic steatosis but not in NASH, and expression of
SREBP1, which is the main transcriptional regulator of FASN, paralleled FASN expression levels in human and experimental NAFLD. In
conclusion, the transcriptional induction of FASN expression in hepatic steatosis is impaired in NASH, while hepatic inflammation in the
absence of steatosis does not affect FASN expression, suggesting that FASN may serve as a new diagnostic marker or therapeutic target for
the progression of NAFLD. (IJCEP1005007).

Key words: Angiosarcoma, pseudomesothelioma, MMP-1, collagenase-1

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Address all correspondence to:
Takeuchi, Tamotsu,  MD
Department of Pathology
Kochi Medical School
Nankoku, Kochi 783-8505, Japan.
Tel/Fax, +81-88-880-2331/-2332