RSS-Feed abonnieren
DOI: 10.1055/s-2004-814151
The Role of the IGF Axis in Hepatocarcinogenesis
Publikationsverlauf
Received 1 September 2003
Accepted after Revision 14 October 2003
Publikationsdatum:
07. Januar 2004 (online)
Abstract
Primary hepatocellular carcinoma (HCC) is one of the most common forms of malignant cancer with the fourth highest mortality rate worldwide. Major risk factors for the development of HCC include chronic infections with the hepatitis B or C virus, alcohol consumption, exposure to dietary aflatoxin B1, hereditary liver disease or liver cirrhosis of any etiology. Recent studies have discovered changes in the insulin-like growth factor (IGF) axis that affect the molecular pathogenesis of HCC, including the autocrine production of IGFs, IGF binding proteins (IGFBPs), IGFBP proteases, and IGF receptor expression. Characteristic alterations detected in HCC and hepatoma cell lines comprise the overexpression of IGF-II and the IGF-I receptor emerging as critical events in malignant transformation and growth of tumors. Simultaneous reduction of IGFBP expression and the increase in proteolytic cleavage of IGFBPs result in an excess of bioactive IGFs. Finally, defective functions of the IGF-II/mannose 6-phosphate receptor involved in degradation of IGF II, the activation of the growth inhibitor TGF-β1, and the lysosomal targeting of cathepsin proteases capable to degrade extracellular matrix proteins may contribute to the development of HCC.
Key words
Insulin-like Growth Factors - IGF Binding Proteins - IGF-I Receptor - IGF-II/ Mannose 6-Phosphate Receptor - Hepatocarcinogenesis - Hepatocellular Carcinoma
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PD Dr. med. J.-G. Scharf, M. D.
Zentrum Innere Medizin, Abteilung Gastroenterologie und Endokrinologie
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