Stem Cells and Cancer in the Liver

The presence of somatic stem cells, which have high proliferative capacity, multipotency (capacity to differentiate into multiple mature cells with different functions) and self-renewal capacity (capacity to maintain the stem cells as themselves by asymmetric division) has been gradually revealed in various digestive organs such as intestines and liver. Although researchers used to be interested in somatic stem cells from the perspective of their application in regenerative medicine, they have recently been attracting much attention in cancer research because their association with carcinogenesis process was elucidated. A number of genes that are involved in self-renewal capacity, namely, “stemness genes”, have been identified through characterization of hematopoietic stem cells and neural stem cells. These genes were found to be involved in the self-renewal of somatic stem cells also in the liver. On the other hand, because these “stemness genes” turned out to be cancer-associated genes, efforts have been made to understand the carcinogenesis and the mechanisms of cancer recurrence and metastasis from the perspective of hierarchy of stem cell system. The hypothesis that the stem/progenitor cells in tissue are the source of cancer development have started to be verified by prospective analysis for tumor initiation using isolated normal stem/progenitor cells. In other words, the concept that, as is the case with the presence of stem cells in normal tissues, cancer stem cells are also present in tumor tissues. Cancer stem cells initiate tumors forming a hierarchy of heterogeneous cancer cells. Here, I will describe the newest findings on hepatic stem/progenitor cells that are attracting attention as a source of the development of hepatocellular carcinoma and cholangiocarcinioma and discuss the association between the self-renewal of hepatic stem cells and the process of malignant transformation.