Published online Oct 7, 2017. doi: 10.3748/wjg.v23.i37.6750
Peer-review started: April 9, 2017
First decision: April 26, 2017
Revised: May 27, 2017
Accepted: July 22, 2017
Article in press: July 24, 2017
Published online: October 7, 2017
Processing time: 180 Days and 5 Hours
Carcinogenic process has been proposed to relay on the capacity to induce local tissue damage and proliferative repair. Liver has a great regeneration capacity and currently, most studies point towards the dominant role of hepatocytes in regeneration at all levels of liver damage. The most frequent liver cancer is hepatocellular carcinoma (HCC). Historical findings originally led to the idea that the cell of origin of HCC might be a progenitor cell. However, current linage tracing studies put the progenitor hypothesis of HCC origin into question. In agreement with their dominant role in liver regeneration, mature hepatocytes are emerging as the cell of origin of HCC, although, the specific hepatocyte subpopulation of origin is yet to be determined. The relationship between the cancer cell of origin (CCO) and cancer-propagating cells, known as hepatic cancer stem cell (HCSC) is unknown. It has been challenging to identify the definitive phenotypic marker of HCSC, probably due to the existence of different cancer stem cells (CSC) subpopulations with different functions within HCC. There is a dynamic interconversion among different CSCs, and between CSC and non-CSCs. Because of that, CSC-state is currently defined as a description of a highly adaptable and dynamic intrinsic property of tumor cells, instead of a static subpopulation of a tumor. Altered conditions could trigger the gain of stemness, some of them include: EMT-MET, epigenetics, microenvironment and selective stimulus such as chemotherapy. This CSC heterogeneity and dynamism makes them out reach from therapeutic protocols directed to a single target. A further avenue of research in this line will be to uncover mechanisms that trigger this interconversion of cell populations within tumors and target it.
Core tip: In agreement with their dominant role in liver regeneration, mature hepatocytes are emerging as the cell of origin of hepatocellular carcinoma. The relationship between the cancer cell of origin (CCO) and hepatic cancer stem cell is unknown. There is a dynamic interconversion among different cancer stem cells (CSCs), and between CSC and non-CSCs. Because of that, CSC-state is currently defined as a description of a highly adaptable and dynamic intrinsic property of tumor cells, instead of a static subpopulation of a tumor. This CSC heterogeneity and dynamism makes them out reach from therapeutic protocols directed to a single target.