Hierarchical potential differentiation of liver cancer stem cells.

Hepatocellular carcinoma (HCC) is one of the most malignant tumors in Chinese people and offers poor prognosis. Tumor tissue, like normal tissue, is hierarchically differentiated. Thus, minor tumor cell populations able to differentiate, such as stem cells, sustain tumor self-renewal and proliferation. The fact that liver cancer stem cells (CSCs) with different surface markers appear heterogeneous with respect to oncogenesis and drug resistance indicates that subpopulations of surface markers preserve the hierarchical potential of differentiation during proliferation, deterioration and relapse. The epithelial to mesenchymal transition (EMT) is correlated to tumor malignancy and aggression, and hepatocytes bearing EMT have obvious hierarchical differentiation potential with respect to signaling pathways such as transforming growth factor β, Wnt/β-catenin and microRNA. Therefore, it may be more effective for early diagnosis to monitor HCC recurrence using peripherally circulating CSCs, and these may also offer potential for HCC immunotherapy or for targeting HCC treatment using these markers. Thus, we reviewed the generation, hierarchical differentiation and clinical application of hepatic CSCs.