Identification of Cancer Stem Cell Subpopulations of CD34+ PLC/PRF/5 That Result in Three Types of Human Liver Carcinomas

CD34+ stem cells play an important role during liver development and regeneration. Thus, we hypothesized that some human liver carcinomas (HLCs) might be derived from transformed CD34+ stem cells. Here, we determined that a population of CD34+ cells isolated from PLC/PRF/5 hepatoma cells (PLC) appears to function as liver cancer stem cells (LCSCs) by forming HLCs in immunodeficient mice with as few as 100 cells. Moreover, the CD34+ PLC subpopulation cells had an advantage over CD34− PLCs at initiating tumors. Three types of HLCs were generated from CD34+ PLC: hepatocellular carcinomas (HCCs); cholangiocarcinomas (CC); and combined hepatocellular cholangiocarcinomas (CHCs). Tumors formed in mice transplanted with 12 subpopulations and 6 progeny subpopulations of CD34+ PLC cells. Interestingly, progenies with certain surface antigens (CD133, CD44, CD90, or EPCAM) predominantly yielded HCCs. CD34+ PLCs that also expressed OV6 and their progeny OV6+ cells primarily produced CHC and CC. This represents the fir...