Lipid oxidation and fibrogenesis in cancer progression

Human hepatocellular carcinoma (HCC) generally develops on the background of chronic inflammation, fibrosis or liver cirrhosis.The risk of cancer development from chronic hepatitis or cirrhosis varies with the degree of fibrosis. the Transforming Growth Factor Beta1 cytokine is strongly linked to tissue fibrosis and can be implicated in tumor development. We studied the synthesis and expression of TGFbeta 1 in the tumour lesions chemically induced in Fisher 344 genetic susceptible rat strains compared to Brown Norway resistant rat strains. TGFbeta1 related cell signal was abolished in susceptible strain; this event was in relationship to the alteration of the activity NADPH oxidase hepatic isoforrms, suggesting a role of pro-oxidant processes in the different susceptibility to hepatocarcinogenesis. TGFbeta1 expression and concomitant loss of its signal pathway in nodules of susceptible strain make the altered hepatocyte clones able to overcome the TGFbeta1 antiproliferative effects, thereby allowing a tumor growth advantage.