Z Gastroenterol 2014; 52 - P_4_20
DOI: 10.1055/s-0033-1360973

Hepatic steatosis enhances growth and invasiveness of hepatocellular carcinoma

A Koch 1, C Dorn 1, M Müller 1, A Bosserhoff 2, C Hellerbrand 1
  • 1University Hospital Regensburg, Department of Internal Medicine I, Regensburg, Germany
  • 2University Regensburg, Institute of Pathology, Regensburg, Germany

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been rising for decades and became a problem of increasing clinical significance worldwide. NAFLD is associated with increased risk of development of end stage liver disease and cirrhosis, and can be complicated by hepatocellular carcinoma (HCC), which became the most common cause of death in patients diagnosed with NAFLD. Moreover, the metabolic syndrome and fatty liver, respectively, are independent risk factors for HCC progression also in other types of chronic liver disease. Still, the underlying mechanisms promoting HCC development and progression in NAFLD are only incompletely understood.

The aim of this study was to establish a model to analyze the influence of hepatic steatosis on hepatic tumor growth.

Methods and Results: We applied a syngeneic, orthotopic HCC model, in which we implanted murine Hepa129 HCC cells orthotopically into the liver of C3 H/He mice, which (i) had been fed with a high-fat diet (HFD) causing significant hepatic steatosis and (ii) control mice, fed with standard chow and normal liver histology. HFD feeding was continued until mice were sacrificed 14 days after tumor cell implantation. Tumors formed in steatotic livers were significantly larger and revealed an invasive growth, while tumors in the control group showed no infiltration in the surrounding liver parenchyma. Notably, tumors formed in steatotic livers also revealed a higher triglyceride content and higher expression of matrix metalloproteases (MMPs). Moreover, expression of the anti-apoptotic gene survivin was significantly increased and tumors grown in steatotic environment revealed less apoptosis than tumors in control livers.

Conclusions: Our data show that feeding a high-fat diet and hepatic steatosis do not only induce the growth but also the invasiveness of HCC cells, indicating the importance of a steatotic environment for HCC progression and offering another option for HCC prevention and treatment.