**5. Experimental models**

#### **5.1 HCC mouse models**

Over decades, different HCC mouse models have been developed.

Chemically induced HCC-models are diverse and not always reproducible. The chemicals usually used are diethylnitrosamine (DEN), peroxisome proliferators, aflatoxine, carbon tetrachloride (CCl4), choline deficient diet or thiacetamide (Heindryckx et al., 2009; Weylandt et al., 2011). Transgenic mouse models were also developed, for example mice that contained HBV or HCV viruses or expressed specifically oncogenes (c-myc, c-myc + E2F1) or growth factors (TGF-, TGF- + c-myc, EGF, FGF19, GMNT, PDGF, 1-antitrypsin) (Heindryckx et al., 2009). Circulating tumor cells were not looked for in any of these animal models. One reason is the huge differences between models and the presence of specific markers for each situation.

In order to solve these problems, researchers developed ectopic implantation that is fast and easy to perform. However, there is still many differences between the cell lines, no direct interaction with the liver tissues and difficulty to export to humans (Heindryckx et al., 2009).
