Increased expression of claudin-1 and claudin-7 in liver cirrhosis and hepatocellular carcinoma.
Claudins have been reported to be differentially regulated in malignancies and implicated in the process of carcinogenesis and tumor progression. Claudin-1 has been described as key factor in the entry of hepatitis C virus (HCV) into hepatocytes and as promoter of epithelial-mesenchymal transition in liver cells. The objective of the current study was to characterize claudin expression in hepatocellular carcinoma (HCC) as well as HCC-surrounding and normal liver samples with respect to cirrhosis and HCV infection. Expression of claudin-1, -2, -3, -4, and -7 was measured by morphometric analysis of immunohistochemistry, and Western blotting in 30 HCCs with 30 corresponding non-tumorous tissues and 6 normal livers. Claudin-1 and -7 protein expression was found significantly elevated in cirrhosis when compared with non-cirrhotic liver. HCCs developed in cirrhotic livers showed even higher expression of claudin-1 contrary to decreased claudin-7 expression when compared with cirrhosis. With reference to HCV status, HCCs or surrounding livers of HCV-infected samples did not show significant alterations in claudin expression when compared with HCV-negative specimens. Cirrhotic transformation associates with elevated claudin-1 and -7 expressions in both non-tumorous liver and HCC. The fact that no significant differences in claudin expression were found regarding HCV-positivity in our sample set suggests that HCV infection alone does not induce a major increase in the total amount of its entry co-factor claudin-1. Increased expression of claudin-1 seems to be a consequence of cirrhotic transformation and might contribute to a more effective HCV entry and malignant transformation.
2nd Department of Pathology, Semmelweis University Budapest, Üllői út 93., 1091, Budapest, Hungary, holczagnes@yahoo.com.
Ágnes
Á
Holczbauer
Benedek
B
Gyöngyösi
Gábor
G
Lotz
Péter
P
Törzsök
Pál
P
Kaposi-Novák
Attila
A
Szijártó
Péter
P
Tátrai
Péter
P
Kupcsulik
Zsuzsa
Z
Schaff
András
A
Kiss
D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D057167:Claudins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis
D015415:Biomarkers; D057167:Claudins