Identification And Characterization Of Cancer Stem Cell In Hepatocellular Carcinoma

Part 1 Identification and characterization of cancer stem cell in hepatocellular carcinomaBoth our previous study and other reports have suggested that CD133,originally classified as a hematopoietic stem cell marker,could be used for enrichment of cancer stem cells(CSCs) in human hepatocellular carcinoma(HCC).It was also noted that not all of CD133~+ cells were representative of CSCs.Further identification and characterization of CSCs or tumor-initiating cells in HCC are necessary to better understand hepatocarcinogenesis.In present study,we demonstrated that CSC phenotype could be precisely defined by co-expression of CD133 and CD44 cell surface markers.CD133~+CD44~+ HCC cells showed stem cell properties,including extensive proliferation,self-renewal and differentiation into the bulk of caneer cells. In vivo xenograft experiments revealed that,actually,the highly tumorigenic capacity of CD133~+ ceils as previously described was primarily attributed to CD133~+CD44~+ cell subpopulation,instead of their CD133~+CD44~- counterparts.Moreover,cells double-positive for CD133 and CD44 exhibited preferential expression of some stem cell-associated genes and were more resistant to chemotherapeutic agents due to the up-regulation of ATP-binding cassette(ABC) superfamily transporters,further supporting these cells as HCC cell origin.Our findings suggest that CD133~+CD44~+ cells might represent true cancer stem/progenitor cells in HCC,which could allow a better understanding of HCC initiation and progression,as well as establish a precise target for the development of more effective therapies. Part 2 Preliminary study on expression profiles of ABC superfamily transporters mediating multidrug resistance in liver cancerMultidrug resistance(MDR),a major cause of cancer chemotherapy failure,is a phenomenon in which cancer cells are resistant to various structurally and mechanistically unrelated chemotherapeutic agents.There are multiple mechanisms responsible for the occurrence of MDR.One of the most common mechanisms is increased drug efflux mediated by ATP-binding cassette(ABC) transporters. Therefore,we examined the expression profiles of several hepatocyte-functional ABC transporters,including ABCB1,ABCB4,ABCC1,ABCC2,ABCC3 and ABCG2,in human liver malignancy by real time RT-PCR and cell immunofluorescent staining. Preliminary research results suggested that these transporters were constitutively expressed to different extents in several liver cancer cell lines,implying their intrinsic drug resistant ability.Furthermore,we found that ABCC2 showed the greatest expression in most of cancer cell lines,providing a solid basis for further exploring its relation to MDR in human liver malignancy.