Road to stemness in hepatocellular carcinoma

Figure 3 An integrated model of cancer cell of origin and cancer stem cell hypotheses in hepatocellular carcinoma. A: Different cells involved in adult liver regeneration are potential targets of malignant transformation when they received hard insults (Yellow ray, i.e. carcinogenic agent, partial hepatectomy). These cells could be considered CCO (Hepatocytes, LSPC, n-SC, HSC), however many studies point to the fact that during severe or chronic damage and consistently in the beginning of HCC, hepatocytes have the main role. The relationship between CCO and CSC is not clear until now. CSCs composition is heterogeneous in HCC tumors. B: The hierarchy hypothesis shows the tumor composition: CSCs and non-CSCs. This includes the plasticity model, which indicates the interconversion by differentiation/dedifferentiation balance between non-CSCs and CSCs. LSPC: Liver stem progenitor cell; n-SC: Normal stem cell; HSC: Hepatic stellar cells.